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Nutrient Sensing at the Plasma Membrane of Fungal Cells

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  • Authors: Patrick Van Dijck1,2, Neil Andrew Brown3, Gustavo H. Goldman4, Julian Rutherford5, Chaoyang Xue6, Griet Van Zeebroeck7,8
  • Editors: Joseph Heitman9, Neil A. R. Gow10
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: VIB-KU Leuven Center for Microbiology KU Leuven, Flanders, Belgium; 2: Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU Leuven, B-3001 Leuven, Belgium; 3: Plant Biology and Crop Science, Rothamsted Research, Harpenden, AL5 2JQ, United Kingdom; 4: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil; 5: Institute for Cell and Molecular Biosciences, Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, United Kingdom; 6: Public Health Research Institute, Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers Biomedical and Health Sciences, Newark, NJ 07103; 7: VIB-KU Leuven Center for Microbiology KU Leuven, Flanders, Belgium; 8: Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU Leuven, B-3001 Leuven, Belgium; 9: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710; 10: School of Medical Sciences, University of Aberdeen, Fosterhill, Aberdeen, AB25 2ZD, United Kingdom
    • Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.FUNK-0031-2016
  • Received 12 November 2016 Accepted 11 December 2016 Published 10 March 2017
  • P. Van Dijck, [email protected]
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  • Abstract:

    To respond to the changing environment, cells must be able to sense external conditions. This is important for many processes including growth, mating, the expression of virulence factors, and several other regulatory effects. Nutrient sensing at the plasma membrane is mediated by different classes of membrane proteins that activate downstream signaling pathways: nontransporting receptors, transceptors, classical and nonclassical G-protein-coupled receptors, and the newly defined extracellular mucin receptors. Nontransporting receptors have the same structure as transport proteins, but have lost the capacity to transport while gaining a receptor function. Transceptors are transporters that also function as a receptor, because they can rapidly activate downstream signaling pathways. In this review, we focus on these four types of fungal membrane proteins. We mainly discuss the sensing mechanisms relating to sugars, ammonium, and amino acids. Mechanisms for other nutrients, such as phosphate and sulfate, are discussed briefly. Because the model yeast has been the most studied, especially regarding these nutrient-sensing systems, each subsection will commence with what is known in this species.

  • Citation: Van Dijck P, Brown N, Goldman G, Rutherford J, Xue C, Van Zeebroeck G. 2017. Nutrient Sensing at the Plasma Membrane of Fungal Cells. Microbiol Spectrum 5(2):FUNK-0031-2016. doi:10.1128/microbiolspec.FUNK-0031-2016.

References

1. Özcan S, Johnston M. 1999. Function and regulation of yeast hexose transporters. Microbiol Mol Biol Rev 63:554–569. [PubMed]
2. Özcan S, Dover J, Rosenwald AG, Wölfl S, Johnston M. 1996. Two glucose transporters in Saccharomyces cerevisiae are glucose sensors that generate a signal for induction of gene expression. Proc Natl Acad Sci USA 93:12428–12432. http://dx.doi.org/10.1073/pnas.93.22.12428 [PubMed]
3. Karhumaa K, Wu B, Kielland-Brandt MC. 2010. Conditions with high intracellular glucose inhibit sensing through glucose sensor Snf3 in Saccharomyces cerevisiae. J Cell Biochem 110:920–925. http://dx.doi.org/10.1002/jcb.22605
4. Cairey-Remonnay A, Deffaud J, Wésolowski-Louvel M, Lemaire M, Soulard A. 2015. Glycolysis controls plasma membrane glucose sensors to promote glucose signaling in yeasts. Mol Cell Biol 35:747–757. http://dx.doi.org/10.1128/MCB.00515-14
5. Özcan S, Dover J, Johnston M. 1998. Glucose sensing and signaling by two glucose receptors in the yeast Saccharomyces cerevisiae. EMBO J 17:2566–2573. http://dx.doi.org/10.1093/emboj/17.9.2566
6. Polish JA, Kim JH, Johnston M. 2005. How the Rgt1 transcription factor of Saccharomyces cerevisiae is regulated by glucose. Genetics 169:583–594. http://dx.doi.org/10.1534/genetics.104.034512
7. Kim JH, Polish J, Johnston M. 2003. Specificity and regulation of DNA binding by the yeast glucose transporter gene repressor Rgt1. Mol Cell Biol 23:5208–5216. http://dx.doi.org/10.1128/MCB.23.15.5208-5216.2003 [PubMed]
8. Palomino A, Herrero P, Moreno F. 2006. Tpk3 and Snf1 protein kinases regulate Rgt1 association with Saccharomyces cerevisiae HXK2 promoter. Nucleic Acids Res 34:1427–1438. http://dx.doi.org/10.1093/nar/gkl028
9. Kaniak A, Xue Z, Macool D, Kim JH, Johnston M. 2004. Regulatory network connecting two glucose signal transduction pathways in Saccharomyces cerevisiae. Eukaryot Cell 3:221–231. http://dx.doi.org/10.1128/EC.3.1.221-231.2004 [PubMed]
10. Moriya H, Johnston M. 2004. Glucose sensing and signaling in Saccharomyces cerevisiae through the Rgt2 glucose sensor and casein kinase I. Proc Natl Acad Sci USA 101:1572–1577. http://dx.doi.org/10.1073/pnas.0305901101
11. Spielewoy N, Flick K, Kalashnikova TI, Walker JR, Wittenberg C. 2004. Regulation and recognition of SCFGrr1 targets in the glucose and amino acid signaling pathways. Mol Cell Biol 24:8994–9005. http://dx.doi.org/10.1128/MCB.24.20.8994-9005.2004 [PubMed]
12. Kim JH, Johnston M. 2006. Two glucose-sensing pathways converge on Rgt1 to regulate expression of glucose transporter genes in Saccharomyces cerevisiae. J Biol Chem 281:26144–26149. http://dx.doi.org/10.1074/jbc.M603636200 [PubMed]
13. Roy A, Jouandot D II, Cho KH, Kim JH. 2014. Understanding the mechanism of glucose-induced relief of Rgt1-mediated repression in yeast. FEBS Open Bio 4:105–111. http://dx.doi.org/10.1016/j.fob.2013.12.004 [PubMed]
14. Betina S, Goffrini P, Ferrero I, Wésolowski-Louvel M. 2001. RAG4 gene encodes a glucose sensor in Kluyveromyces lactis. Genetics 158:541–548. [PubMed]
15. Chen XJ, Wésolowski-Louvel M, Fukuhara H. 1992. Glucose transport in the yeast Kluyveromyces lactis. II. Transcriptional regulation of the glucose transporter gene RAG1. Mol Gen Genet 233:97–105. http://dx.doi.org/10.1007/BF00587566
16. Blaisonneau J, Fukuhara H, Wésolowski-Louvel M. 1997. The Kluyveromyces lactis equivalent of casein kinase I is required for the transcription of the gene encoding the low-affinity glucose permease. Mol Gen Genet 253:469–477. http://dx.doi.org/10.1007/s004380050345
17. Hnatova M, Wésolowski-Louvel M, Dieppois G, Deffaud J, Lemaire M. 2008. Characterization of KlGRR1 and SMS1 genes, two new elements of the glucose signaling pathway of Kluyveromyces lactis. Eukaryot Cell 7:1299–1308. http://dx.doi.org/10.1128/EC.00454-07
18. Cotton P, Soulard A, Wésolowski-Louvel M, Lemaire M. 2012. The SWI/SNF KlSnf2 subunit controls the glucose signaling pathway to coordinate glycolysis and glucose transport in Kluyveromyces lactis. Eukaryot Cell 11:1382–1390. http://dx.doi.org/10.1128/EC.00210-12
19. Stasyk OG, Maidan MM, Stasyk OV, Van Dijck P, Thevelein JM, Sibirny AA. 2008. Identification of hexose transporter-like sensor HXS1 and functional hexose transporter HXT1 in the methylotrophic yeast Hansenula polymorpha. Eukaryot Cell 7:735–746. http://dx.doi.org/10.1128/EC.00028-08 [PubMed]
20. Fan J, Chaturvedi V, Shen SH. 2002. Identification and phylogenetic analysis of a glucose transporter gene family from the human pathogenic yeast Candida albicans. J Mol Evol 55:336–346. http://dx.doi.org/10.1007/s00239-002-2330-4 [PubMed]
21. Brown V, Sexton JA, Johnston M. 2006. A glucose sensor in Candida albicans. Eukaryot Cell 5:1726–1737. http://dx.doi.org/10.1128/EC.00186-06 [PubMed][CrossRef]
22. Sabina J, Brown V. 2009. Glucose sensing network in Candida albicans: a sweet spot for fungal morphogenesis. Eukaryot Cell 8:1314–1320. http://dx.doi.org/10.1128/EC.00138-09
23. Bahn YS, Xue C, Idnurm A, Rutherford JC, Heitman J, Cardenas ME. 2007. Sensing the environment: lessons from fungi. Nat Rev Microbiol 5:57–69. http://dx.doi.org/10.1038/nrmicro1578 [PubMed]
24. Liu TB, Wang Y, Baker GM, Fahmy H, Jiang L, Xue C. 2013. The glucose sensor-like protein Hxs1 is a high-affinity glucose transporter and required for virulence in Cryptococcus neoformans. PLoS One 8:e64239. http://dx.doi.org/10.1371/journal.pone.0064239
25. Xue C. 2012. Cryptococcus and beyond--inositol utilization and its implications for the emergence of fungal virulence. PLoS Pathog 8:e1002869. http://dx.doi.org/10.1371/journal.ppat.1002869 [PubMed]
26. Healy ME, Dillavou CL, Taylor GE. 1977. Diagnostic medium containing inositol, urea, and caffeic acid for selective growth of Cryptococcus neoformans. J Clin Microbiol 6:387–391. [PubMed]
27. Xue C, Tada Y, Dong X, Heitman J. 2007. The human fungal pathogen Cryptococcus can complete its sexual cycle during a pathogenic association with plants. Cell Host Microbe 1:263–273. http://dx.doi.org/10.1016/j.chom.2007.05.005 [PubMed]
28. Fisher SK, Novak JE, Agranoff BW. 2002. Inositol and higher inositol phosphates in neural tissues: homeostasis, metabolism and functional significance. J Neurochem 82:736–754. http://dx.doi.org/10.1046/j.1471-4159.2002.01041.x
29. Xue C, Liu T, Chen L, Li W, Liu I, Kronstad JW, Seyfang A, Heitman J. 2010. Role of an expanded inositol transporter repertoire in Cryptococcus neoformans sexual reproduction and virulence. MBio 1:e00084-10. http://dx.doi.org/10.1128/mBio.00084-10
30. Liu TB, Subbian S, Pan W, Eugenin E, Xie J, Xue C. 2014. Cryptococcus inositol utilization modulates the host protective immune response during brain infection. Cell Commun Signal 12:51. http://dx.doi.org/10.1186/s12964-014-0051-0
31. Liu TB, Kim JC, Wang Y, Toffaletti DL, Eugenin E, Perfect JR, Kim KJ, Xue C. 2013. Brain inositol is a novel stimulator for promoting Cryptococcus penetration of the blood-brain barrier. PLoS Pathog 9:e1003247. http://dx.doi.org/10.1371/journal.ppat.1003247
32. Wang Y, Liu TB, Delmas G, Park S, Perlin D, Xue C. 2011. Two major inositol transporters and their role in cryptococcal virulence. Eukaryot Cell 10:618–628. http://dx.doi.org/10.1128/EC.00327-10 [PubMed]
33. Brown NA, Ries LNA, Goldman GH. 2014. How nutritional status signalling coordinates metabolism and lignocellulolytic enzyme secretion. Fungal Genet Biol 72:48–63. http://dx.doi.org/10.1016/j.fgb.2014.06.012
34. Zhang W, Kou Y, Xu J, Cao Y, Zhao G, Shao J, Wang H, Wang Z, Bao X, Chen G, Liu W. 2013. Two major facilitator superfamily sugar transporters from Trichoderma reesei and their roles in induction of cellulase biosynthesis. J Biol Chem 288:32861–32872. http://dx.doi.org/10.1074/jbc.M113.505826 [PubMed]
35. Znameroski EA, Coradetti ST, Roche CM, Tsai JC, Iavarone AT, Cate JHD, Glass NL. 2012. Induction of lignocellulose-degrading enzymes in Neurospora crassa by cellodextrins. Proc Natl Acad Sci USA 109:6012–6017. http://dx.doi.org/10.1073/pnas.1118440109
36. Cai P, Wang B, Ji J, Jiang Y, Wan L, Tian C, Ma Y. 2015. The putative cellodextrin transporter-like protein CLP1 is involved in cellulase induction in Neurospora crassa. J Biol Chem 290:788–796. http://dx.doi.org/10.1074/jbc.M114.609875 [PubMed]
37. Forsberg H, Ljungdahl PO. 2001. Sensors of extracellular nutrients in Saccharomyces cerevisiae. Curr Genet 40:91–109. http://dx.doi.org/10.1007/s002940100244 [PubMed]
38. Kodama Y, Omura F, Takahashi K, Shirahige K, Ashikari T. 2002. Genome-wide expression analysis of genes affected by amino acid sensor Ssy1p in Saccharomyces cerevisiae. Curr Genet 41:63–72. http://dx.doi.org/10.1007/s00294-002-0291-1 [PubMed]
39. Klasson H, Fink GR, Ljungdahl PO. 1999. Ssy1p and Ptr3p are plasma membrane components of a yeast system that senses extracellular amino acids. Mol Cell Biol 19:5405–5416. http://dx.doi.org/10.1128/MCB.19.8.5405
40. Wu B, Ottow K, Poulsen P, Gaber RF, Albers E, Kielland-Brandt MC. 2006. Competitive intra- and extracellular nutrient sensing by the transporter homologue Ssy1p. J Cell Biol 173:327–331. http://dx.doi.org/10.1083/jcb.200602089 [PubMed]
41. Gaber RF, Ottow K, Andersen HA, Kielland-Brandt MC. 2003. Constitutive and hyperresponsive signaling by mutant forms of Saccharomyces cerevisiae amino acid sensor Ssy1. Eukaryot Cell 2:922–929. http://dx.doi.org/10.1128/EC.2.5.922-929.2003
42. Poulsen P, Gaber RF, Kielland-Brandt MC. 2008. Hyper- and hyporesponsive mutant forms of the Saccharomyces cerevisiae Ssy1 amino acid sensor. Mol Membr Biol 25:164–176. http://dx.doi.org/10.1080/09687680701771917 [PubMed]
43. Souciet J, Aigle M, Artiguenave F, Blandin G, Bolotin-Fukuhara M, Bon E, Brottier P, Casaregola S, de Montigny J, Dujon B, Durrens P, Gaillardin C, Lépingle A, Llorente B, Malpertuy A, Neuvéglise C, Ozier-Kalogéropoulos O, Potier S, Saurin W, Tekaia F, Toffano-Nioche C, Wésolowski-Louvel M, Wincker P, Weissenbach J. 2000. Genomic exploration of the hemiascomycetous yeasts: 1. A set of yeast species for molecular evolution studies. FEBS Lett 487:3–12. http://dx.doi.org/10.1016/S0014-5793(00)02272-9
44. Liu Z, Thornton J, Spírek M, Butow RA. 2008. Activation of the SPS amino acid-sensing pathway in Saccharomyces cerevisiae correlates with the phosphorylation state of a sensor component, Ptr3. Mol Cell Biol 28:551–563. http://dx.doi.org/10.1128/MCB.00929-07
45. Omnus DJ, Ljungdahl PO. 2013. Rts1-protein phosphatase 2A antagonizes Ptr3-mediated activation of the signaling protease Ssy5 by casein kinase I. Mol Biol Cell 24:1480–1492. http://dx.doi.org/10.1091/mbc.E13-01-0019
46. Maggio R, Innamorati G, Parenti M. 2007. G protein-coupled receptor oligomerization provides the framework for signal discrimination. J Neurochem 103:1741–1752. http://dx.doi.org/10.1111/j.1471-4159.2007.04896.x
47. Lemmon MA, Schlessinger J. 2010. Cell signaling by receptor tyrosine kinases. Cell 141:1117–1134. http://dx.doi.org/10.1016/j.cell.2010.06.011 [PubMed]
48. Andréasson C, Heessen S, Ljungdahl PO. 2006. Regulation of transcription factor latency by receptor-activated proteolysis. Genes Dev 20:1563–1568. http://dx.doi.org/10.1101/gad.374206 [PubMed]
49. Pfirrmann T, Heessen S, Omnus DJ, Andréasson C, Ljungdahl PO. 2010. The prodomain of Ssy5 protease controls receptor-activated proteolysis of transcription factor Stp1. Mol Cell Biol 30:3299–3309. http://dx.doi.org/10.1128/MCB.00323-10
50. Abdel-Sater F, Jean C, Merhi A, Vissers S, André B. 2011. Amino acid signaling in yeast: activation of Ssy5 protease is associated with its phosphorylation-induced ubiquitylation. J Biol Chem 286:12006–12015. http://dx.doi.org/10.1074/jbc.M110.200592
51. Omnus DJ, Pfirrmann T, Andréasson C, Ljungdahl PO. 2011. A phosphodegron controls nutrient-induced proteasomal activation of the signaling protease Ssy5. Mol Biol Cell 22:2754–2765. http://dx.doi.org/10.1091/mbc.E11-04-0282 [PubMed]
52. Johnston M, Kim JH. 2005. Glucose as a hormone: receptor-mediated glucose sensing in the yeast Saccharomyces cerevisiae. Biochem Soc Trans 33:247–252. http://dx.doi.org/10.1042/BST0330247
53. Andréasson C, Ljungdahl PO. 2002. Receptor-mediated endoproteolytic activation of two transcription factors in yeast. Genes Dev 16:3158–3172. http://dx.doi.org/10.1101/gad.239202
54. Wielemans K, Jean C, Vissers S, André B. 2010. Amino acid signaling in yeast: post-genome duplication divergence of the Stp1 and Stp2 transcription factors. J Biol Chem 285:855–865. http://dx.doi.org/10.1074/jbc.M109.015263
55. Tumusiime S, Zhang C, Overstreet MS, Liu Z. 2011. Differential regulation of transcription factors Stp1 and Stp2 in the Ssy1-Ptr3-Ssy5 amino acid sensing pathway. J Biol Chem 286:4620–4631. http://dx.doi.org/10.1074/jbc.M110.195313 [PubMed]
56. Eckert-Boulet N, Larsson K, Wu B, Poulsen P, Regenberg B, Nielsen J, Kielland-Brandt MC. 2006. Deletion of RTS1, encoding a regulatory subunit of protein phosphatase 2A, results in constitutive amino acid signaling via increased Stp1p processing. Eukaryot Cell 5:174–179. http://dx.doi.org/10.1128/EC.5.1.174-179.2006
57. Andréasson C, Ljungdahl PO. 2004. The N-terminal regulatory domain of Stp1p is modular and, fused to an artificial transcription factor, confers full Ssy1p-Ptr3p-Ssy5p sensor control. Mol Cell Biol 24:7503–7513. http://dx.doi.org/10.1128/MCB.24.17.7503-7513.2004
58. Boban M, Ljungdahl PO. 2007. Dal81 enhances Stp1- and Stp2-dependent transcription necessitating negative modulation by inner nuclear membrane protein Asi1 in Saccharomyces cerevisiae. Genetics 176:2087–2097. http://dx.doi.org/10.1534/genetics.107.075077
59. Omnus DJ, Ljungdahl PO. 2014. Latency of transcription factor Stp1 depends on a modular regulatory motif that functions as cytoplasmic retention determinant and nuclear degron. Mol Biol Cell 25:3823–3833. http://dx.doi.org/10.1091/mbc.E14-06-1140
60. Shin CS, Kim SY, Huh WK. 2009. TORC1 controls degradation of the transcription factor Stp1, a key effector of the SPS amino-acid-sensing pathway in Saccharomyces cerevisiae. J Cell Sci 122:2089–2099. http://dx.doi.org/10.1242/jcs.047191
61. Brega E, Zufferey R, Mamoun CB. 2004. Candida albicans Csy1p is a nutrient sensor important for activation of amino acid uptake and hyphal morphogenesis. Eukaryot Cell 3:135–143. http://dx.doi.org/10.1128/EC.3.1.135-143.2004
62. Martínez P, Ljungdahl PO. 2004. An ER packaging chaperone determines the amino acid uptake capacity and virulence of Candida albicans. Mol Microbiol 51:371–384. http://dx.doi.org/10.1046/j.1365-2958.2003.03845.x [PubMed]
63. Martínez P, Ljungdahl PO. 2005. Divergence of Stp1 and Stp2 transcription factors in Candida albicans places virulence factors required for proper nutrient acquisition under amino acid control. Mol Cell Biol 25:9435–9446. http://dx.doi.org/10.1128/MCB.25.21.9435-9446.2005
64. Dabas N, Morschhäuser J. 2008. A transcription factor regulatory cascade controls secreted aspartic protease expression in Candida albicans. Mol Microbiol 69:586–602. http://dx.doi.org/10.1111/j.1365-2958.2008.06297.x
65. Davis MM, Alvarez FJ, Ryman K, Holm ÅA, Ljungdahl PO, Engström Y. 2011. Wild-type Drosophila melanogaster as a model host to analyze nitrogen source dependent virulence of Candida albicans. PLoS One 6:e27434. http://dx.doi.org/10.1371/journal.pone.0027434
66. Fernandes JD, Martho K, Tofik V, Vallim MA, Pascon RC. 2015. The role of amino acid permeases and tryptophan biosynthesis in Cryptococcus neoformans survival. PLoS One 10:e0132369. http://dx.doi.org/10.1371/journal.pone.0132369
67. Reifenberger E, Boles E, Ciriacy M. 1997. Kinetic characterization of individual hexose transporters of Saccharomyces cerevisiae and their relation to the triggering mechanisms of glucose repression. Eur J Biochem 245:324–333. http://dx.doi.org/10.1111/j.1432-1033.1997.00324.x
68. Bandyopadhyay G, Sajan MP, Kanoh Y, Standaert ML, Burke TRJ Jr, Quon MJ, Reed BC, Dikic I, Noel LE, Newgard CB, Farese R. 2000. Glucose activates mitogen-activated protein kinase (extracellular signal-regulated kinase) through proline-rich tyrosine kinase-2 and the Glut1 glucose transporter. J Biol Chem 275:40817–40826. http://dx.doi.org/10.1074/jbc.M007920200 [PubMed]
69. Guillemain G, Loizeau M, Pinçon-Raymond M, Girard J, Leturque A. 2000. The large intracytoplasmic loop of the glucose transporter GLUT2 is involved in glucose signaling in hepatic cells. J Cell Sci 113:841–847. [PubMed]
70. Stolarczyk E, Guissard C, Michau A, Even PC, Grosfeld A, Serradas P, Lorsignol A, Pénicaud L, Brot-Laroche E, Leturque A, Le Gall M. 2010. Detection of extracellular glucose by GLUT2 contributes to hypothalamic control of food intake. Am J Physiol Endocrinol Metab 298:E1078–E1087. http://dx.doi.org/10.1152/ajpendo.00737.2009
71. Shewan AM, McCann RK, Lamb CA, Stirrat L, Kioumourtzoglou D, Adamson IS, Verma S, James DE, Bryant NJ. 2013. Endosomal sorting of GLUT4 and Gap1 is conserved between yeast and insulin-sensitive cells. J Cell Sci 126:1576–1582. http://dx.doi.org/10.1242/jcs.114371
72. Luo L, Tong X, Farley PC. 2007. The Candida albicans gene HGT12 (orf19.7094) encodes a hexose transporter. FEMS Immunol Med Microbiol 51:14–17. http://dx.doi.org/10.1111/j.1574-695X.2007.00274.x [PubMed]
73. Luongo M, Porta A, Maresca B. 2005. Homology, disruption and phenotypic analysis of CaGS Candida albicans gene induced during macrophage infection. FEMS Immunol Med Microbiol 45:471–478. http://dx.doi.org/10.1016/j.femsim.2005.06.007
74. Stasyk OV, Stasyk OG, Komduur J, Veenhuis M, Cregg JM, Sibirny AA. 2004. A hexose transporter homologue controls glucose repression in the methylotrophic yeast Hansenula polymorpha. J Biol Chem 279:8116–8125. http://dx.doi.org/10.1074/jbc.M310960200
75. Madi L, McBride SA, Bailey LA, Ebbole DJ. 1997. rco-3, a gene involved in glucose transport and conidiation in Neurospora crassa. Genetics 146:499–508. [PubMed]
76. Lingner U, Münch S, Deising HB, Sauer N. 2011. Hexose transporters of a hemibiotrophic plant pathogen: functional variations and regulatory differences at different stages of infection. J Biol Chem 286:20913–20922. http://dx.doi.org/10.1074/jbc.M110.213678
77. Schuler D, Wahl R, Wippel K, Vranes M, Münsterkötter M, Sauer N, Kämper J. 2015. Hxt1, a monosaccharide transporter and sensor required for virulence of the maize pathogen Ustilago maydis. New Phytol 206:1086–1100. http://dx.doi.org/10.1111/nph.13314
78. Znameroski EA, Li X, Tsai JC, Galazka JM, Glass NL, Cate JHD. 2014. Evidence for transceptor function of cellodextrin transporters in Neurospora crassa. J Biol Chem 289:2610–2619. http://dx.doi.org/10.1074/jbc.M113.533273 [PubMed]
79. Galazka JM, Tian C, Beeson WT, Martinez B, Glass NL, Cate JHD. 2010. Cellodextrin transport in yeast for improved biofuel production. Science 330:84–86. http://dx.doi.org/10.1126/science.1192838 [PubMed]
80. Ha S-J, Galazka JM, Kim SR, Choi J-H, Yang X, Seo J-H, Glass NL, Cate JHD, Jin Y-S. 2011. Engineered Saccharomyces cerevisiae capable of simultaneous cellobiose and xylose fermentation. Proc Natl Acad Sci USA 108:504–509. http://dx.doi.org/10.1073/pnas.1010456108
81. Regenberg B, Düring-Olsen L, Kielland-Brandt MC, Holmberg S. 1999. Substrate specificity and gene expression of the amino-acid permeases in Saccharomyces cerevisiae. Curr Genet 36:317–328. http://dx.doi.org/10.1007/s002940050506 [PubMed]
82. Jauniaux JC, Grenson M. 1990. GAP1, the general amino acid permease gene of Saccharomyces cerevisiae. Nucleotide sequence, protein similarity with the other bakers yeast amino acid permeases, and nitrogen catabolite repression. Eur J Biochem 190:39–44. http://dx.doi.org/10.1111/j.1432-1033.1990.tb15542.x
83. Uemura T, Kashiwagi K, Igarashi K. 2005. Uptake of putrescine and spermidine by Gap1p on the plasma membrane in Saccharomyces cerevisiae. Biochem Biophys Res Commun 328:1028–1033. http://dx.doi.org/10.1016/j.bbrc.2005.01.064 [PubMed]
84. Hofman-Bang J. 1999. Nitrogen catabolite repression in Saccharomyces cerevisiae. Mol Biotechnol 12:35–71. http://dx.doi.org/10.1385/MB:12:1:35 [PubMed]
85. Magasanik B, Kaiser CA. 2002. Nitrogen regulation in Saccharomyces cerevisiae. Gene 290:1–18. http://dx.doi.org/10.1016/S0378-1119(02)00558-9
86. De Craene JO, Soetens O, André B. 2001. The Npr1 kinase controls biosynthetic and endocytic sorting of the yeast Gap1 permease. J Biol Chem 276:43939–43948. http://dx.doi.org/10.1074/jbc.M102944200 [PubMed]
87. Soetens O, De Craene JO, André B. 2001. Ubiquitin is required for sorting to the vacuole of the yeast general amino acid permease, Gap1. J Biol Chem 276:43949–43957. http://dx.doi.org/10.1074/jbc.M102945200 [PubMed]
88. O’Donnell AF, Apffel A, Gardner RG, Cyert MS. 2010. Alpha-arrestins Aly1 and Aly2 regulate intracellular trafficking in response to nutrient signaling. Mol Biol Cell 21:3552–3566. http://dx.doi.org/10.1091/mbc.E10-07-0636
89. Merhi A, Gérard N, Lauwers E, Prévost M, André B. 2011. Systematic mutational analysis of the intracellular regions of yeast Gap1 permease. PLoS One 6:e18457. http://dx.doi.org/10.1371/journal.pone.0018457
90. Van Zeebroeck G, Rubio-Texeira M, Schothorst J, Thevelein JM. 2014. Specific analogues uncouple transport, signalling, oligo-ubiquitination and endocytosis in the yeast Gap1 amino acid transceptor. Mol Microbiol 93:213–233. http://dx.doi.org/10.1111/mmi.12654
91. Risinger AL, Cain NE, Chen EJ, Kaiser CA. 2006. Activity-dependent reversible inactivation of the general amino acid permease. Mol Biol Cell 17:4411–4419. http://dx.doi.org/10.1091/mbc.E06-06-0506 [PubMed]
92. Donaton MC, Holsbeeks I, Lagatie O, Van Zeebroeck G, Crauwels M, Winderickx J, Thevelein JM. 2003. The Gap1 general amino acid permease acts as an amino acid sensor for activation of protein kinase A targets in the yeast Saccharomyces cerevisiae. Mol Microbiol 50:911–929. http://dx.doi.org/10.1046/j.1365-2958.2003.03732.x
93. Van Zeebroeck G, Bonini BM, Versele M, Thevelein JM. 2009. Transport and signaling via the amino acid binding site of the yeast Gap1 amino acid transceptor. Nat Chem Biol 5:45–52. http://dx.doi.org/10.1038/nchembio.132 [PubMed]
94. Crauwels M, Donaton MC, Pernambuco MB, Winderickx J, de Winde JH, Thevelein JM. 1997. The Sch9 protein kinase in the yeast Saccharomyces cerevisiae controls cAPK activity and is required for nitrogen activation of the fermentable-growth-medium-induced (FGM) pathway. Microbiology 143:2627–2637. http://dx.doi.org/10.1099/00221287-143-8-2627
95. Voordeckers K, Kimpe M, Haesendonckx S, Louwet W, Versele M, Thevelein JM. 2011. Yeast 3-phosphoinositide-dependent protein kinase-1 (PDK1) orthologs Pkh1-3 differentially regulate phosphorylation of protein kinase A (PKA) and the protein kinase B (PKB)/S6K ortholog Sch9. J Biol Chem 286:22017–22027. http://dx.doi.org/10.1074/jbc.M110.200071
96. Hirimburegama K, Durnez P, Keleman J, Oris E, Vergauwen R, Mergelsberg H, Thevelein JM. 1992. Nutrient-induced activation of trehalase in nutrient-starved cells of the yeast Saccharomyces cerevisiae: cAMP is not involved as second messenger. J Gen Microbiol 138:2035–2043. http://dx.doi.org/10.1099/00221287-138-10-2035
97. Kraidlova L, Van Zeebroeck G, Van Dijck P, Sychrová H. 2011. The Candida albicans GAP gene family encodes permeases involved in general and specific amino acid uptake and sensing. Eukaryot Cell 10:1219–1229. http://dx.doi.org/10.1128/EC.05026-11
98. Marini AM, Soussi-Boudekou S, Vissers S, André B. 1997. A family of ammonium transporters in Saccharomyces cerevisiae. Mol Cell Biol 17:4282–4293. http://dx.doi.org/10.1128/MCB.17.8.4282 [PubMed]
99. Dubois E, Grenson M. 1979. Methylamine/ammonia uptake systems in Saccharomyces cerevisiae: multiplicity and regulation. Mol Gen Genet 175:67–76. http://dx.doi.org/10.1007/BF00267857
100. Lorenz MC, Heitman J. 1998. The MEP2 ammonium permease regulates pseudohyphal differentiation in Saccharomyces cerevisiae. EMBO J 17:1236–1247. http://dx.doi.org/10.1093/emboj/17.5.1236
101. Biswas K, Morschhäuser J. 2005. The Mep2p ammonium permease controls nitrogen starvation-induced filamentous growth in Candida albicans. Mol Microbiol 56:649–669. http://dx.doi.org/10.1111/j.1365-2958.2005.04576.x
102. Smith DG, Garcia-Pedrajas MD, Gold SE, Perlin MH. 2003. Isolation and characterization from pathogenic fungi of genes encoding ammonium permeases and their roles in dimorphism. Mol Microbiol 50:259–275. http://dx.doi.org/10.1046/j.1365-2958.2003.03680.x
103. Rutherford JC, Lin X, Nielsen K, Heitman J. 2008. Amt2 permease is required to induce ammonium-responsive invasive growth and mating in Cryptococcus neoformans. Eukaryot Cell 7:237–246. http://dx.doi.org/10.1128/EC.00079-07 [PubMed]
104. Mitsuzawa H. 2006. Ammonium transporter genes in the fission yeast Schizosaccharomyces pombe: role in ammonium uptake and a morphological transition. Genes Cells 11:1183–1195. http://dx.doi.org/10.1111/j.1365-2443.2006.01014.x [PubMed]
105. Van Nuland A, Vandormael P, Donaton M, Alenquer M, Lourenço A, Quintino E, Versele M, Thevelein JM. 2006. Ammonium permease-based sensing mechanism for rapid ammonium activation of the protein kinase A pathway in yeast. Mol Microbiol 59:1485–1505. http://dx.doi.org/10.1111/j.1365-2958.2005.05043.x [PubMed]
106. Cardenas ME, Cutler NS, Lorenz MC, Di Como CJ, Heitman J. 1999. The TOR signaling cascade regulates gene expression in response to nutrients. Genes Dev 13:3271–3279. http://dx.doi.org/10.1101/gad.13.24.3271 [PubMed]
107. Boeckstaens M, André B, Marini AM. 2007. The yeast ammonium transport protein Mep2 and its positive regulator, the Npr1 kinase, play an important role in normal and pseudohyphal growth on various nitrogen media through retrieval of excreted ammonium. Mol Microbiol 64:534–546. http://dx.doi.org/10.1111/j.1365-2958.2007.05681.x
108. van den Berg B, Chembath A, Jefferies D, Basle A, Khalid S, Rutherford JC. 2016. Structural basis for Mep2 ammonium transceptor activation by phosphorylation. Nat Commun 7:11337. http://dx.doi.org/10.1038/ncomms11337 [PubMed]
109. Khademi S, O’Connell J III, Remis J, Robles-Colmenares Y, Miercke LJW, Stroud RM. 2004. Mechanism of ammonia transport by Amt/MEP/Rh: structure of AmtB at 1.35 A. Science 305:1587–1594. http://dx.doi.org/10.1126/science.1101952 [PubMed]
110. Andrade SL, Dickmanns A, Ficner R, Einsle O. 2005. Crystal structure of the archaeal ammonium transporter Amt-1 from Archaeoglobus fulgidus. Proc Natl Acad Sci USA 102:14994–14999. http://dx.doi.org/10.1073/pnas.0506254102 [PubMed]
111. Zheng L, Kostrewa D, Bernèche S, Winkler FK, Li XD. 2004. The mechanism of ammonia transport based on the crystal structure of AmtB of Escherichia coli. Proc Natl Acad Sci USA 101:17090–17095. http://dx.doi.org/10.1073/pnas.0406475101
112. Gruswitz F, Chaudhary S, Ho JD, Schlessinger A, Pezeshki B, Ho CM, Sali A, Westhoff CM, Stroud RM. 2010. Function of human Rh based on structure of RhCG at 2.1 A. Proc Natl Acad Sci USA 107:9638–9643. http://dx.doi.org/10.1073/pnas.1003587107 [PubMed]
113. Lin Y, Cao Z, Mo Y. 2006. Molecular dynamics simulations on the Escherichia coli ammonia channel protein AmtB: mechanism of ammonia/ammonium transport. J Am Chem Soc 128:10876–10884. http://dx.doi.org/10.1021/ja0631549 [PubMed]
114. Nygaard TP, Rovira C, Peters GH, Jensen MØ. 2006. Ammonium recruitment and ammonia transport by E. coli ammonia channel AmtB. Biophys J 91:4401–4412. http://dx.doi.org/10.1529/biophysj.106.089714 [PubMed]
115. Lamoureux G, Javelle A, Baday S, Wang S, Bernèche S. 2010. Transport mechanisms in the ammonium transporter family. Transfus Clin Biol 17:168–175. http://dx.doi.org/10.1016/j.tracli.2010.06.004 [PubMed]
116. Wang S, Orabi EA, Baday S, Bernèche S, Lamoureux G. 2012. Ammonium transporters achieve charge transfer by fragmenting their substrate. J Am Chem Soc 134:10419–10427. http://dx.doi.org/10.1021/ja300129x [PubMed]
117. Boeckstaens M, André B, Marini AM. 2008. Distinct transport mechanisms in yeast ammonium transport/sensor proteins of the Mep/Amt/Rh family and impact on filamentation. J Biol Chem 283:21362–21370. http://dx.doi.org/10.1074/jbc.M801467200
118. Rutherford JC, Chua G, Hughes T, Cardenas ME, Heitman J. 2008. A Mep2-dependent transcriptional profile links permease function to gene expression during pseudohyphal growth in Saccharomyces cerevisiae. Mol Biol Cell 19:3028–3039. http://dx.doi.org/10.1091/mbc.E08-01-0033
119. Paul JA, Barati MT, Cooper M, Perlin MH. 2014. Physical and genetic interaction between ammonium transporters and the signaling protein Rho1 in the plant pathogen Ustilago maydis. Eukaryot Cell 13:1328–1336. http://dx.doi.org/10.1128/EC.00150-14
120. Teichert S, Rutherford JC, Wottawa M, Heitman J, Tudzynski B. 2008. Impact of ammonium permeases mepA, mepB, and mepC on nitrogen-regulated secondary metabolism in Fusarium fujikuroi. Eukaryot Cell 7:187–201. http://dx.doi.org/10.1128/EC.00351-07
121. Javelle A, Morel M, Rodríguez-Pastrana BR, Botton B, André B, Marini AM, Brun A, Chalot M. 2003. Molecular characterization, function and regulation of ammonium transporters (Amt) and ammonium-metabolizing enzymes (GS, NADP-GDH) in the ectomycorrhizal fungus Hebeloma cylindrosporum. Mol Microbiol 47:411–430. http://dx.doi.org/10.1046/j.1365-2958.2003.03303.x [PubMed]
122. Shnaiderman C, Miyara I, Kobiler I, Sherman A, Prusky D. 2013. Differential activation of ammonium transporters during the accumulation of ammonia by Colletotrichum gloeosporioides and its effect on appressoria formation and pathogenicity. Mol Plant Microbe Interact 26:345–355. http://dx.doi.org/10.1094/MPMI-07-12-0170-R
123. Li L, Wright SJ, Krystofova S, Park G, Borkovich KA. 2007. Heterotrimeric G protein signaling in filamentous fungi. Annu Rev Microbiol 61:423–452. http://dx.doi.org/10.1146/annurev.micro.61.080706.093432 [PubMed]
124. Thevelein JM, de Winde JH. 1999. Novel sensing mechanisms and targets for the cAMP-protein kinase A pathway in the yeast Saccharomyces cerevisiae. Mol Microbiol 33:904–918. http://dx.doi.org/10.1046/j.1365-2958.1999.01538.x [PubMed]
125. Lemaire K, Van de Velde S, Van Dijck P, Thevelein JM. 2004. Glucose and sucrose act as agonist and mannose as antagonist ligands of the G protein-coupled receptor Gpr1 in the yeast Saccharomyces cerevisiae. Mol Cell 16:293–299. http://dx.doi.org/10.1016/j.molcel.2004.10.004
126. Yun C-W, Tamaki H, Nakayama R, Yamamoto K, Kumagai H. 1998. Gpr1p, a putative G-protein coupled receptor, regulates glucose-dependent cellular cAMP level in yeast Saccharomyces cerevisiae. Biochem Biophys Res Commun 252:29–33. http://dx.doi.org/10.1006/bbrc.1998.9600
127. Rolland F, De Winde JH, Lemaire K, Boles E, Thevelein JM, Winderickx J. 2000. Glucose-induced cAMP signalling in yeast requires both a G-protein coupled receptor system for extracellular glucose detection and a separable hexose kinase-dependent sensing process. Mol Microbiol 38:348–358. http://dx.doi.org/10.1046/j.1365-2958.2000.02125.x
128. Broach JR, Deschenes RJ. 1990. The function of ras genes in Saccharomyces cerevisiae. Adv Cancer Res 54:79–139. http://dx.doi.org/10.1016/S0065-230X(08)60809-X
129. Colombo S, Ma P, Cauwenberg L, Winderickx J, Crauwels M, Teunissen A, Nauwelaers D, de Winde JH, Gorwa MF, Colavizza D, Thevelein JM. 1998. Involvement of distinct G-proteins, Gpa2 and Ras, in glucose- and intracellular acidification-induced cAMP signalling in the yeast Saccharomyces cerevisiae. EMBO J 17:3326–3341. http://dx.doi.org/10.1093/emboj/17.12.3326 [PubMed]
130. Versele M, de Winde JH, Thevelein JM. 1999. A novel regulator of G protein signalling in yeast, Rgs2, downregulates glucose-activation of the cAMP pathway through direct inhibition of Gpa2. EMBO J 18:5577–5591. http://dx.doi.org/10.1093/emboj/18.20.5577
131. Lorenz MC, Pan X, Harashima T, Cardenas ME, Xue Y, Hirsch JP, Heitman J. 2000. The G protein-coupled receptor gpr1 is a nutrient sensor that regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Genetics 154:609–622. [PubMed]
132. Johnson C, Kweon HK, Sheidy D, Shively CA, Mellacheruvu D, Nesvizhskii AI, Andrews PC, Kumar A. 2014. The yeast Sks1p kinase signaling network regulates pseudohyphal growth and glucose response. PLoS Genet 10:e1004183. http://dx.doi.org/10.1371/journal.pgen.1004183
133. Harashima T, Heitman J. 2002. The Gα protein Gpa2 controls yeast differentiation by interacting with kelch repeat proteins that mimic Gβ subunits. Mol Cell 10:163–173. http://dx.doi.org/10.1016/S1097-2765(02)00569-5
134. Niranjan T, Guo X, Victor J, Lu A, Hirsch JP. 2007. Kelch repeat protein interacts with the yeast Gα subunit Gpa2p at a site that couples receptor binding to guanine nucleotide exchange. J Biol Chem 282:24231–24238. http://dx.doi.org/10.1074/jbc.M702595200
135. Zeller CE, Parnell SC, Dohlman HG. 2007. The RACK1 ortholog Asc1 functions as a G-protein beta subunit coupled to glucose responsiveness in yeast. J Biol Chem 282:25168–25176. http://dx.doi.org/10.1074/jbc.M702569200 [PubMed]
136. Peeters T, Louwet W, Geladé R, Nauwelaers D, Thevelein JM, Versele M. 2006. Kelch-repeat proteins interacting with the G α protein Gpa2 bypass adenylate cyclase for direct regulation of protein kinase A in yeast. Proc Natl Acad Sci USA 103:13034–13039. http://dx.doi.org/10.1073/pnas.0509644103 [PubMed]
137. Budhwar R, Fang G, Hirsch JP. 2011. Kelch repeat proteins control yeast PKA activity in response to nutrient availability. Cell Cycle 10:767–770. http://dx.doi.org/10.4161/cc.10.5.14828 [PubMed]
138. Budhwar R, Lu A, Hirsch JP. 2010. Nutrient control of yeast PKA activity involves opposing effects on phosphorylation of the Bcy1 regulatory subunit. Mol Biol Cell 21:3749–3758. http://dx.doi.org/10.1091/mbc.E10-05-0388 [PubMed]
139. Willhite DG, Brigati JR, Selcer KE, Denny JE, Duck ZA, Wright SE. 2014. Pheromone responsiveness is regulated by components of the Gpr1p-mediated glucose sensing pathway in Saccharomyces cerevisiae. Yeast 31:361–374. http://dx.doi.org/10.1002/yea.3030
140. Van Dijck P. 2009. Nutrient sensing G protein-coupled receptors: interesting targets for antifungals? Med Mycol 47:671–680. http://dx.doi.org/10.3109/13693780802713349 [PubMed]
141. Maidan MM, De Rop L, Serneels J, Exler S, Rupp S, Tournu H, Thevelein JM, Van Dijck P. 2005. The G protein-coupled receptor Gpr1 and the Gα protein Gpa2 act through the cAMP-protein kinase A pathway to induce morphogenesis in Candida albicans. Mol Biol Cell 16:1971–1986. http://dx.doi.org/10.1091/mbc.E04-09-0780
142. Miwa T, Takagi Y, Shinozaki M, Yun C-W, Schell WA, Perfect JR, Kumagai H, Tamaki H. 2004. Gpr1, a putative G-protein-coupled receptor, regulates morphogenesis and hypha formation in the pathogenic fungus Candida albicans. Eukaryot Cell 3:919–931. http://dx.doi.org/10.1128/EC.3.4.919-931.2004 [PubMed]
143. Maidan MM, Thevelein JM, Van Dijck P. 2005. Carbon source induced yeast-to-hypha transition in Candida albicans is dependent on the presence of amino acids and on the G-protein-coupled receptor Gpr1. Biochem Soc Trans 33:291–293. http://dx.doi.org/10.1042/BST0330291
144. Kozubowski L, Lee SC, Heitman J. 2009. Signalling pathways in the pathogenesis of Cryptococcus. Cell Microbiol 11:370–380. http://dx.doi.org/10.1111/j.1462-5822.2008.01273.x [PubMed]
145. Xue C, Bahn YS, Cox GM, Heitman J. 2006. G protein-coupled receptor Gpr4 senses amino acids and activates the cAMP-PKA pathway in Cryptococcus neoformans. Mol Biol Cell 17:667–679. http://dx.doi.org/10.1091/mbc.E05-07-0699 [PubMed]
146. Okagaki LH, Wang Y, Ballou ER, O’Meara TR, Bahn YS, Alspaugh JA, Xue C, Nielsen K. 2011. Cryptococcal titan cell formation is regulated by G-protein signaling in response to multiple stimuli. Eukaryot Cell 10:1306–1316. http://dx.doi.org/10.1128/EC.05179-11
147. Li L, Borkovich KA. 2006. GPR-4 is a predicted G-protein-coupled receptor required for carbon source-dependent asexual growth and development in Neurospora crassa. Eukaryot Cell 5:1287–1300. http://dx.doi.org/10.1128/EC.00109-06 [PubMed]
148. de Souza WR, Morais ER, Krohn NG, Savoldi M, Goldman MHS, Rodrigues F, Caldana C, Semelka CT, Tikunov AP, Macdonald JM, Goldman GH. 2013. Identification of metabolic pathways influenced by the G-protein coupled receptors GprB and BprD in Aspergillus nidulans. PLoS One 8:e62088. http://dx.doi.org/10.1371/journal.pone.0062088
149. Han KH, Seo JA, Yu JH. 2004. A putative G protein-coupled receptor negatively controls sexual development in Aspergillus nidulans. Mol Microbiol 51:1333–1345. http://dx.doi.org/10.1111/j.1365-2958.2003.03940.x
150. Brown NA, Dos Reis TF, Ries LNA, Caldana C, Mah J-H, Yu J-H, Macdonald JM, Goldman GH. 2015. G-protein coupled receptor-mediated nutrient sensing and developmental control in Aspergillus nidulans. Mol Microbiol 98:420–439. http://dx.doi.org/10.1111/mmi.13135
151. Gehrke A, Heinekamp T, Jacobsen ID, Brakhage AA. 2010. Heptahelical receptors GprC and GprD of Aspergillus fumigatus are essential regulators of colony growth, hyphal morphogenesis, and virulence. Appl Environ Microbiol 76:3989–3998. http://dx.doi.org/10.1128/AEM.00052-10
152. Affeldt KJ, Carrig J, Amare M, Keller NP. 2014. Global survey of canonical Aspergillus flavus G protein-coupled receptors. MBio 5:e01501-14. http://dx.doi.org/10.1128/mBio.01501-14
153. Krohn NG, Brown NA, Colabardini AC, Reis T, Savoldi M, Dinamarco TM, Goldman MHS, Goldman GH. 2014. The Aspergillus nidulans ATM kinase regulates mitochondrial function, glucose uptake and the carbon starvation response. G3 (Bethesda) 4:49–62. http://dx.doi.org/10.1534/g3.113.008607 [PubMed]
154. Krystofova S, Borkovich KA. 2006. The predicted G-protein-coupled receptor GPR-1 is required for female sexual development in the multicellular fungus Neurospora crassa. Eukaryot Cell 5:1503–1516. http://dx.doi.org/10.1128/EC.00124-06 [PubMed]
155. Chung KS, Won M, Lee SB, Jang YJ, Hoe KL, Kim DU, Lee JW, Kim KW, Yoo HS. 2001. Isolation of a novel gene from Schizosaccharomyces pombe: stm1 + encoding a seven-transmembrane loop protein that may couple with the heterotrimeric Gα2 protein, Gpa2. J Biol Chem 276:40190–40201. http://dx.doi.org/10.1074/jbc.M100341200
156. Rispail N, Soanes DM, Ant C, Czajkowski R, Grünler A, Huguet R, Perez-Nadales E, Poli A, Sartorel E, Valiante V, Yang M, Beffa R, Brakhage AA, Gow NAR, Kahmann R, Lebrun M-H, Lenasi H, Perez-Martin J, Talbot NJ, Wendland J, Di Pietro A. 2009. Comparative genomics of MAP kinase and calcium-calcineurin signalling components in plant and human pathogenic fungi. Fungal Genet Biol 46:287–298. http://dx.doi.org/10.1016/j.fgb.2009.01.002
157. Turrà D, El Ghalid M, Rossi F, Di Pietro A. 2015. Fungal pathogen uses sex pheromone receptor for chemotropic sensing of host plant signals. Nature 527:521–524. http://dx.doi.org/10.1038/nature15516
158. DeZwaan TM, Carroll AM, Valent B, Sweigard JA. 1999. Magnaporthe grisea pth11p is a novel plasma membrane protein that mediates appressorium differentiation in response to inductive substrate cues. Plant Cell 11:2013–2030. http://dx.doi.org/10.1105/tpc.11.10.2013
159. Ramanujam R, Calvert ME, Selvaraj P, Naqvi NI. 2013. The late endosomal HOPS complex anchors active G-protein signaling essential for pathogenesis in Magnaporthe oryzae. PLoS Pathog 9:e1003527. http://dx.doi.org/10.1371/journal.ppat.1003527
160. Kulkarni RD, Thon MR, Pan H, Dean RA. 2005. Novel G-protein-coupled receptor-like proteins in the plant pathogenic fungus Magnaporthe grisea. Genome Biol 6:R24. http://dx.doi.org/10.1186/gb-2005-6-3-r24 [PubMed]
161. Cabrera IE, Pacentine IV, Lim A, Guerrero N, Krystofova S, Li L, Michkov AV, Servin JA, Ahrendt SR, Carrillo AJ, Davidson LM, Barsoum AH, Cao J, Castillo R, Chen W-C, Dinkchian A, Kim S, Kitada SM, Lai TH, Mach A, Malekyan C, Moua TR, Torres CR, Yamamoto A, Borkovich KA. 2015. Global analysis of predicted G protein-coupled receptor genes in the filamentous fungus, Neurospora crassa. G3 (Bethesda) 5:2729–2743. http://dx.doi.org/10.1534/g3.115.020974
162. Cullen PJ, Sabbagh W Jr, Graham E, Irick MM, van Olden EK, Neal C, Delrow J, Bardwell L, Sprague GF Jr. 2004. A signaling mucin at the head of the Cdc42- and MAPK-dependent filamentous growth pathway in yeast. Genes Dev 18:1695–1708. http://dx.doi.org/10.1101/gad.1178604
163. Cullen PJ, Sprague GF Jr. 2000. Glucose depletion causes haploid invasive growth in yeast. Proc Natl Acad Sci USA 97:13619–13624. http://dx.doi.org/10.1073/pnas.240345197 [PubMed]
164. Karunanithi S, Cullen PJ. 2012. The filamentous growth MAPK pathway responds to glucose starvation through the Mig1/2 transcriptional repressors in Saccharomyces cerevisiae. Genetics 192:869–887. http://dx.doi.org/10.1534/genetics.112.142661
165. Karunanithi S, Joshi J, Chavel C, Birkaya B, Grell L, Cullen PJ. 2012. Regulation of mat responses by a differentiation MAPK pathway in Saccharomyces cerevisiae. PLoS One 7:e32294. http://dx.doi.org/10.1371/journal.pone.0032294 [PubMed]
166. Cullen PJ. 2007. Signaling mucins: the new kids on the MAPK block. Crit Rev Eukaryot Gene Expr 17:241–257. http://dx.doi.org/10.1615/CritRevEukarGeneExpr.v17.i3.50 [PubMed]
167. Vadaie N, Dionne H, Akajagbor DS, Nickerson SR, Krysan DJ, Cullen PJ. 2008. Cleavage of the signaling mucin Msb2 by the aspartyl protease Yps1 is required for MAPK activation in yeast. J Cell Biol 181:1073–1081. http://dx.doi.org/10.1083/jcb.200704079 [PubMed]
168. Verstrepen KJ, Klis FM. 2006. Flocculation, adhesion and biofilm formation in yeasts. Mol Microbiol 60:5–15. http://dx.doi.org/10.1111/j.1365-2958.2006.05072.x [PubMed]
169. Guo B, Styles CA, Feng Q, Fink GR. 2000. A Saccharomyces gene family involved in invasive growth, cell-cell adhesion, and mating. Proc Natl Acad Sci USA 97:12158–12163. http://dx.doi.org/10.1073/pnas.220420397 [PubMed]
170. Finkel JS, Mitchell AP. 2011. Genetic control of Candida albicans biofilm development. Nat Rev Microbiol 9:109–118. http://dx.doi.org/10.1038/nrmicro2475 [PubMed]
171. Román E, Cottier F, Ernst JF, Pla J. 2009. Msb2 signaling mucin controls activation of Cek1 mitogen-activated protein kinase in Candida albicans. Eukaryot Cell 8:1235–1249. http://dx.doi.org/10.1128/EC.00081-09
172. Puri S, Kumar R, Chadha S, Tati S, Conti HR, Hube B, Cullen PJ, Edgerton M. 2012. Secreted aspartic protease cleavage of Candida albicans Msb2 activates Cek1 MAPK signaling affecting biofilm formation and oropharyngeal candidiasis. PLoS One 7:e46020. (Erratum, 8(8), 2013.) http://dx.doi.org/10.1371/journal.pone.0046020
173. Szafranski-Schneider E, Swidergall M, Cottier F, Tielker D, Román E, Pla J, Ernst JF. 2012. Msb2 shedding protects Candida albicans against antimicrobial peptides. PLoS Pathog 8:e1002501. http://dx.doi.org/10.1371/journal.ppat.1002501
174. Swidergall M, Ernst AM, Ernst JF. 2013. Candida albicans mucin Msb2 is a broad-range protectant against antimicrobial peptides. Antimicrob Agents Chemother 57:3917–3922. http://dx.doi.org/10.1128/AAC.00862-13
175. Brown NA, Dos Reis TF, Goinski AB, Savoldi M, Menino J, Almeida MT, Rodrigues F, Goldman GH. 2014. The Aspergillus nidulans signalling mucin MsbA regulates starvation responses, adhesion and affects cellulase secretion in response to environmental cues. Mol Microbiol 94:1103–1120. http://dx.doi.org/10.1111/mmi.12820
176. Pérez-Nadales E, Di Pietro A. 2011. The membrane mucin Msb2 regulates invasive growth and plant infection in Fusarium oxysporum. Plant Cell 23:1171–1185. http://dx.doi.org/10.1105/tpc.110.075093
177. Perez-Nadales E, Di Pietro A. 2015. The transmembrane protein Sho1 cooperates with the mucin Msb2 to regulate invasive growth and plant infection in Fusarium oxysporum. Mol Plant Pathol 16:593–603. http://dx.doi.org/10.1111/mpp.12217
178. Lanver D, Berndt P, Tollot M, Naik V, Vranes M, Warmann T, Münch K, Rössel N, Kahmann R. 2014. Plant surface cues prime Ustilago maydis for biotrophic development. PLoS Pathog 10:e1004272. http://dx.doi.org/10.1371/journal.ppat.1004272
179. Lanver D, Mendoza-Mendoza A, Brachmann A, Kahmann R. 2010. Sho1 and Msb2-related proteins regulate appressorium development in the smut fungus Ustilago maydis. Plant Cell 22:2085–2101. http://dx.doi.org/10.1105/tpc.109.073734 [PubMed]
180. Liu W, Zhou X, Li G, Li L, Kong L, Wang C, Zhang H, Xu J-R. 2011. Multiple plant surface signals are sensed by different mechanisms in the rice blast fungus for appressorium formation. PLoS Pathog 7:e1001261. http://dx.doi.org/10.1371/journal.ppat.1001261
181. Wang G, Li G, Zhang S, Jiang C, Qin J, Xu J-R. 2015. Activation of the signalling mucin MoMsb2 and its functional relationship with Cbp1 in Magnaporthe oryzae. Environ Microbiol 17:2969–2981. http://dx.doi.org/10.1111/1462-2920.12847
182. Kamakura T, Yamaguchi S, Saitoh K, Teraoka T, Yamaguchi I. 2002. A novel gene, CBP1, encoding a putative extracellular chitin-binding protein, may play an important role in the hydrophobic surface sensing of Magnaporthe grisea during appressorium differentiation. Mol Plant Microbe Interact 15:437–444. http://dx.doi.org/10.1094/MPMI.2002.15.5.437
183. Weisman R. 2016. Target of rapamycin (TOR) regulates growth in response to nutritional signals. Microbiol Spectrum 4(5) :FUNK-0006-2016. [PubMed]
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/content/journal/microbiolspec/10.1128/microbiolspec.FUNK-0031-2016
2017-03-10
2021-04-10

Abstract:

To respond to the changing environment, cells must be able to sense external conditions. This is important for many processes including growth, mating, the expression of virulence factors, and several other regulatory effects. Nutrient sensing at the plasma membrane is mediated by different classes of membrane proteins that activate downstream signaling pathways: nontransporting receptors, transceptors, classical and nonclassical G-protein-coupled receptors, and the newly defined extracellular mucin receptors. Nontransporting receptors have the same structure as transport proteins, but have lost the capacity to transport while gaining a receptor function. Transceptors are transporters that also function as a receptor, because they can rapidly activate downstream signaling pathways. In this review, we focus on these four types of fungal membrane proteins. We mainly discuss the sensing mechanisms relating to sugars, ammonium, and amino acids. Mechanisms for other nutrients, such as phosphate and sulfate, are discussed briefly. Because the model yeast has been the most studied, especially regarding these nutrient-sensing systems, each subsection will commence with what is known in this species.

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Nutrient Sensing at the Plasma Membrane of Fungal Cells
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Citation: Van Dijck P, Brown N, Goldman G, Rutherford J, Xue C, Van Zeebroeck G. 2017. Nutrient sensing at the plasma membrane of fungal cells. microbiolspec 5(2): doi:10.1128/microbiolspec.FUNK-0031-2016
/content/microbiolspec/10.1128/microbiolspec.FUNK-0031-2016.fig1
FIGURE 1
Sugar-sensing proteins in the plasma membrane of fungal cells. Nutrient-sensing proteins in general can be divided into nontransporting receptors, transceptors, and G-protein-coupled receptors (GPCRs). Nontransporting sugar receptors include the () glucose sensors Snf3/Rgt2, the () glucose sensor Rag4, the () glucose sensor Hxs1, the () glucose sensor Hgt4, the () inositol sensor Itr1, the () cellobiose sensor Crt1, and the cellodextrin sensor Clp1. Sugar transceptors include the glucose sensor Hgt12, the hexose sensors Hxs1/2, the hexose sensor Gcr1, the () sugar sensor Rco3, the () hexose sensor Hxt4, the () hexose sensor Hxt1, the cellobiose sensors Cdt1/2, and the () cellobiose sensor Stp1. Sugar GPCRs include the glucose sensor Gpr1, the glucose sensors Gpr4/5, the glucose sensor Gpr4, the () glucose sensors GprD/H, the () glucose sensors GprC/D, and the () glucose sensors GprA/C/J/K/R.
microbiolspec/5/2/FUNK-0031-2016-fig1_thmb.gif
microbiolspec/5/2/FUNK-0031-2016-fig1.gif
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FIGURE 1

Sugar-sensing proteins in the plasma membrane of fungal cells. Nutrient-sensing proteins in general can be divided into nontransporting receptors, transceptors, and G-protein-coupled receptors (GPCRs). Nontransporting sugar receptors include the () glucose sensors Snf3/Rgt2, the () glucose sensor Rag4, the () glucose sensor Hxs1, the () glucose sensor Hgt4, the () inositol sensor Itr1, the () cellobiose sensor Crt1, and the cellodextrin sensor Clp1. Sugar transceptors include the glucose sensor Hgt12, the hexose sensors Hxs1/2, the hexose sensor Gcr1, the () sugar sensor Rco3, the () hexose sensor Hxt4, the () hexose sensor Hxt1, the cellobiose sensors Cdt1/2, and the () cellobiose sensor Stp1. Sugar GPCRs include the glucose sensor Gpr1, the glucose sensors Gpr4/5, the glucose sensor Gpr4, the () glucose sensors GprD/H, the () glucose sensors GprC/D, and the () glucose sensors GprA/C/J/K/R.

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.FUNK-0031-2016
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FIGURE 2
Nitrogen-sensing proteins in the plasma membrane of fungal cells. Nutrient-sensing proteins, in general, can be divided into nontransporting receptors, transceptors, and G-protein-coupled receptors (GPCRs). Nontransporting nitrogen receptors include the () amino acid sensor Ssy1, the () amino acid sensor Csy1, and an unknown () amino acid sensor. Nitrogen transceptors include the amino acid sensor Gap1, the amino acid sensors Gap1/2/6, the ammonium sensor Mep2, the ammonium sensor Mep2, the () ammonium sensor Ump2, the () ammonium sensors MepA-C, the () ammonium sensors Amt1-3, the () ammonium sensor Amt1, and the () ammonium sensors MepA-C. Nitrogen GPCRs include the methionine sensor Gpr1, the amino acid sensor Gpr4, the () tryptophan sensor GprH, the () proline sensor GprC/D, the () nitrogen sensor Stm1, and the ammonium sensor GprR.
microbiolspec/5/2/FUNK-0031-2016-fig2_thmb.gif
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FIGURE 2

Nitrogen-sensing proteins in the plasma membrane of fungal cells. Nutrient-sensing proteins, in general, can be divided into nontransporting receptors, transceptors, and G-protein-coupled receptors (GPCRs). Nontransporting nitrogen receptors include the () amino acid sensor Ssy1, the () amino acid sensor Csy1, and an unknown () amino acid sensor. Nitrogen transceptors include the amino acid sensor Gap1, the amino acid sensors Gap1/2/6, the ammonium sensor Mep2, the ammonium sensor Mep2, the () ammonium sensor Ump2, the () ammonium sensors MepA-C, the () ammonium sensors Amt1-3, the () ammonium sensor Amt1, and the () ammonium sensors MepA-C. Nitrogen GPCRs include the methionine sensor Gpr1, the amino acid sensor Gpr4, the () tryptophan sensor GprH, the () proline sensor GprC/D, the () nitrogen sensor Stm1, and the ammonium sensor GprR.

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.FUNK-0031-2016
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FIGURE 3
Surface-sensing proteins in the plasma membrane of fungal cells. Characterized surface-sensing proteins can be divided into G-protein-coupled receptors (GPCRs) and the interacting Sho receptors and the extracellular mucin receptors. The nonclassical, Pth11-type, GPCRs include the () Pth11 receptor of hydrophobic surfaces and the () Gpr32, Gpr36, and Gpr39 putative lignocellulose receptors. The Sho receptors include the orthologous (), () and , hydrophobic surface Sho1 receptors. The extracellular mucins include the orthologous (), , , , Msb2 hydrophobic surface receptors, in addition to the Msb2 receptors of () and () that have not been characterized as detecting surfaces, plus the additional Cbp1 mucin receptor of hydrophobic surfaces from .
microbiolspec/5/2/FUNK-0031-2016-fig3_thmb.gif
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FIGURE 3

Surface-sensing proteins in the plasma membrane of fungal cells. Characterized surface-sensing proteins can be divided into G-protein-coupled receptors (GPCRs) and the interacting Sho receptors and the extracellular mucin receptors. The nonclassical, Pth11-type, GPCRs include the () Pth11 receptor of hydrophobic surfaces and the () Gpr32, Gpr36, and Gpr39 putative lignocellulose receptors. The Sho receptors include the orthologous (), () and , hydrophobic surface Sho1 receptors. The extracellular mucins include the orthologous (), , , , Msb2 hydrophobic surface receptors, in addition to the Msb2 receptors of () and () that have not been characterized as detecting surfaces, plus the additional Cbp1 mucin receptor of hydrophobic surfaces from .

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.FUNK-0031-2016
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FIGURE 4
Nutrient- and surface-sensing proteins in the plasma membrane of fungal cells and the downstream signal transduction pathways they trigger. Examples for the different classes of nutrient (nontransporting receptors, transceptors, and GPCRs) and surface (mucin and Sho) sensing proteins are shown. Sensing of nutrients by nontransporting receptors and sugar transceptors results in the induction of nutrient transporter genes. Nitrogen transceptors (e.g., Gap1) result in the activation of the PKA pathway upon sensing appropriate nitrogen sources. Depending on the type of GPCR, they can activate the cAMP-PKA pathway, the MAPK pathway, or both. The surface receptors activate the MAPK pathway.
microbiolspec/5/2/FUNK-0031-2016-fig4_thmb.gif
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FIGURE 4

Nutrient- and surface-sensing proteins in the plasma membrane of fungal cells and the downstream signal transduction pathways they trigger. Examples for the different classes of nutrient (nontransporting receptors, transceptors, and GPCRs) and surface (mucin and Sho) sensing proteins are shown. Sensing of nutrients by nontransporting receptors and sugar transceptors results in the induction of nutrient transporter genes. Nitrogen transceptors (e.g., Gap1) result in the activation of the PKA pathway upon sensing appropriate nitrogen sources. Depending on the type of GPCR, they can activate the cAMP-PKA pathway, the MAPK pathway, or both. The surface receptors activate the MAPK pathway.

Source: microbiolspec March 2017 vol. 5 no. 2 doi:10.1128/microbiolspec.FUNK-0031-2016
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