1887

Chapter 12 : G-Protein Signaling Pathways: Regulating Morphogenesis and Virulence of

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Ebook: Choose a downloadable PDF or ePub file. Chapter is a downloadable PDF file. File must be downloaded within 48 hours of purchase

Buy this Chapter
Digital (?) $15.00

Preview this chapter:
Zoom in
Zoomout

G-Protein Signaling Pathways: Regulating Morphogenesis and Virulence of , Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816858/9781555815011_Chap12-1.gif /docserver/preview/fulltext/10.1128/9781555816858/9781555815011_Chap12-2.gif

Abstract:

This chapter addresses the roles of heterotrimeric and monomeric G proteins in the growth and development of . The central motifs of the cAMP signal transduction pathway are highly conserved in eukaryotes, allowing diverse cell types to respond to different environmental stresses. However, the role of this pathway in microbial virulence was not predicted in studies involving nonpathogenic model organisms. Additionally, fungal pathogens of plants, such as the maize pathogen and the rice blast fungus , use cAMP pathways to regulate morphogenesis and virulence. Alternatively, overproduction of intracellular cyclic AMP (cAMP) may also impair virulence through mechanisms such as stress tolerance modulation. Studies of RGS proteins in have revealed that the regulation of G-protein signaling is more intricate and potentially more complicated than in . The NRG1 ortholog represses the transcription of several genes required for the yeast-hyphal transition, and this gene is required for virulence. Several of the capsule and melanin genes whose transcription is controlled by cAMP do not appear to be targets of Nrg1. Additionally, the altered capsule phenotype of the nrg1 mutant strain is less severe than the acapsular phenotype of strains with defective cAMP signaling. Lastly, melanin is not significantly altered in the nrg1 mutant. The cAMP signal transduction pathway plays a central role in the stress response and virulence of microbial pathogens. Animal modeling of cryptococcal infection with MATα and MATa strains suggest that MATα strains are intrinsically more virulent.

Citation: Alspaugh J, Nichols C, Xue C, Shen W, Wang P. 2011. G-Protein Signaling Pathways: Regulating Morphogenesis and Virulence of , p 153-165. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch12

Key Concept Ranking

Sodium Dodecyl Sulfate
0.43200976
0.43200976
Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

Model of heterotrimeric G-protein signaling. Upon activation of the upstream GPCR (R), the Goc protein exchanges GDP for GTP, resulting in a dissociation of the a, β, and y subunits and subsequent activation of the downstream signal transduction pathways.

Citation: Alspaugh J, Nichols C, Xue C, Shen W, Wang P. 2011. G-Protein Signaling Pathways: Regulating Morphogenesis and Virulence of , p 153-165. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch12
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

Pka1 and Pkr1 are two components of the PKA holoenzyme. (A) In the presence of cAMP, the dimeric regulatory subunits of PKA (Pkr1) dissociate from the catalytic sub-units (Pka1), allowing downstream transmission of the cAMP signal. (B) The wild-type (WT), mutant, mutant, and double mutant strains were assessed for melanin production by incubation on Niger seed medium for 5 days. A mutation constitutively activates downstream effectors of this pathway, restoring melanin to the mutant ( ).

Citation: Alspaugh J, Nichols C, Xue C, Shen W, Wang P. 2011. G-Protein Signaling Pathways: Regulating Morphogenesis and Virulence of , p 153-165. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch12
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3
FIGURE 3

Model of the Gpa1/cAMP signaling pathway ( ).

Citation: Alspaugh J, Nichols C, Xue C, Shen W, Wang P. 2011. G-Protein Signaling Pathways: Regulating Morphogenesis and Virulence of , p 153-165. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch12
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4
FIGURE 4

Model of the Ras1 pathway. The downstream signaling specificity of the Ras1 protein is largely determined by its subcellular localization. Ras1 farnesylation (thin wavy line) is required for all protein functions, and this posttranslational modification is sufficient to direct the protein to the endomembranes and support mating. In contrast, Ras1 palmitoylation (thick straight line) is required to localize Ras1 to the plasma membrane, and this modification is required to activate the Ras1 morphogenesis pathway.

Citation: Alspaugh J, Nichols C, Xue C, Shen W, Wang P. 2011. G-Protein Signaling Pathways: Regulating Morphogenesis and Virulence of , p 153-165. In Heitman J, Kozel T, Kwon-Chung K, Perfect J, Casadevall A (ed), . ASM Press, Washington, DC. doi: 10.1128/9781555816858.ch12
Permissions and Reprints Request Permissions
Download as Powerpoint

References

/content/book/10.1128/9781555816858.ch12
1. Alspaugh, J. A.,, L. M. Cavallo,, J. R. Perfect, and, J. Heitman. 2000. RAS1 regulates filamentation, mating and growth at high temperature of Cryptococcus neoformans. Mol. Microbiol. 36:352365.
2. Alspaugh, J. A.,, R.C. Davidson, and, J. Heitman. 2000. Morphogenesis of Cryptococcus neoformans, p. 217238. In J. F. Ernst, and, A. Schmidt (ed.), Dimorphism in Human Pathogenic and Apathogenic Yeasts, Contributions to Microbiology, vol. 5. Karger, Basel, Switzerland.
3. Alspaugh, J. A.,, J.R. Perfect, and, J. Heitman. 1997. Cryptococcus neoformans mating and virulence are regulated by the G-protein alpha subunit GPA1 and cAMP. Genes Dev. 11:32063217.
4. Alspaugh, J. A.,, R. Pukkila-Worley,, T. Harashima,, L. M. Cavallo,, D. Funnell,, G. M. Cox,, J. R. Perfect,, J. W. Kronstad, and, J. Heitman. 2002. Adenylyl cyclase functions downstream of the G-alpha protein Gpa1 and controls mating and pathogenicity of Cryptococcus neoformans. Eukaryot. Cell 1:7584.
5. Bahn, Y. S.,, J.K. Hicks,, S. S. Giles,, G. M. Cox, and, J. Heitman. 2004. Adenylyl cyclase-associated protein Aca1 regulates virulence and differentiation of Cryptococcus neoformans via the cyclic AMP-protein kinase A cascade. Eukaryot. Cell 3:14761491.
6. Bahn, Y. S.,, C. Xue,, A. Idnurm,, J. C. Rutherford,, J. Heitman, and, M. E. Cardenas. 2007. Sensing the environment: lessons from fungi. Nat. Rev. 5:5769.
7. Bakkeren, G., J. Kamper, and, J. Schirawski. 2008. Sex in smut fungi: structure, function and evolution of mating-type complexes. Fungal Genet. Biol. 45 (Suppl. 1):S15–S21.
8. Ballon, D. R.,, P. L. Flanary,, D. P. Gladue,, J. B. Konopka,, H. G. Dohlman, and, J. Thorner. 2006. DEPdomain-mediated regulation of GPCR signaling responses. Cell 126:10791093.
9. Bardwell, L. 2004. A walk-through of the yeast mating pheromone response pathway. Peptides 25:14651476.
10. Batlle, M.,, A. Lu,, D.A. Green,, Y. Xue, and, J. P. Hirsch. 2003. Krh1p and Krh2p act downstream of the Gpa2p G(alpha) subunit to negatively regulate haploid invasive growth. J. Cell Sci. 116:701710.
11. Berkey, C. D.,, V.K. Vyas, and, M. Carlson. 2004. Nrg1 and Nrg2 transcriptional repressors are differently regulated in response to carbon source. Eukaryot. Cell 3:311317.
12. Braun, B. R.,, D. Kadosh, and, A. D. Johnson. 2001. NRG1, a repressor of filamentous growth in C. albicans, is down-regulated during filament induction. EMBO J. 20:47534761.
13. Broach, J. R., and, R. J. Deschenes. 1990. The functions of RAS genes in Saccharomyces cerevisiae. Adv. Cancer Res. 54:79138.
14. Burkholder, A. C., and, L. H. Hartwell. 1985. The yeast alpha-factor receptor: structural properties deduced from the sequence of the STE2 gene. Nucleic Acids Res. 13:84638475.
15. Casselton, L. A. 2002. Mate recognition in fungi. Heredity 88:142147.
16. Chang, E. C., and, M. R. Philips. 2006. Spatial segregation of Ras signaling: new evidence from fission yeast. Cell Cycle 5:19361939.
17. Chang, Y. C.,, G. F. Miller, and, K. J. Kwon-Chung. 2003. Importance of a developmentally regulated pheromone receptor of Cryptococcus neoformans for virulence. Infect. Immun. 71:49534960.
18. Chang, Y. C.,, L. A. Penoyer, and, K. J. Kwon-Chung. 2001. The second STE12 homologue of Cryptococcus neoformans is MATa-specific and plays an important role in virulence. Proc. Natl. Acad. Sci. USA 98:32583263.
19. Chang, Y. C.,, B.L. Wickes,, G. F. Miller,, L. A. Penoyer, and, K. J. Kwon-Chung. 2000. Cryptococcus neoformans Ste12alpha regulates virulence but is not essential for mating. J. Exp. Med. 191:871882.
20. Chang, Y. C.,, L.C. Wright,, R.L. Tscharke,, T. C Sorrell,, C. F. Wilson, and, K. J. Kwon-Chung. 2004. Regulatory roles for the homeodomain and C2H2 zinc finger regions of Cryptococcus neoformans Ste12alphap. Mol. Microbiol. 53:13851396.
21. Choi, W., and, R. A. Dean. 1997. The adenylate cyclase gene MAC1 of Magnaporthe grisea controls appressorium formation and other aspects of growth and development. Plant Cell 9:19731983.
22. Chung, S.,, M. Karos,, Y.C. Chang,, J. Lukszo,, B. L. Wickes, and, K. J. Kwon-Chung. 2002. Molecular analysis of CPRalpha, a MATalpha-specific pheromone receptor gene of Cryptococcus neoformans. Eukaryot. Cell 1:432439.
23. Clapham, D. E., and, E. J. Neer. 1993. New roles for G-protein beta gamma-dimers in transmembrane signalling. Nature 365:403406.
24. Clapham, D. E., and, E. J. Neer. 1997. G protein beta gamma subunits. Annu. Rev. Pharmacol. Toxicol. 37:167203.
25. Clarke, D. L.,, G.L. Woodlee,, C. M. McClelland,, T. S. Seymour, and, B. L. Wickes. 2001. The Cryptococcus neoformans STE11alpha gene is similar to other fungal mitogen-activated protein kinase kinase kinase (MAPKKK) genes but is mating type specific. Mol. Microbiol. 40:200213.
26. Cole, G. M., and, S. I. Reed. 1992. Pheromone-induced phosphorylation of a G protein β subunit in S. cerevisiae is associated with an adaptive response to mating pheromone. Cell 64:703716.
27. Cramer, K. L.,, Q.D. Gerrald,, C. B. Nichols,, M. S. Price, and, J. A. Alspaugh. 2006. The transcription factor Nrg1 mediates capsule, stress response, and pathogenesis in Cryptococcus neoformans. Eukaryot. Cell 5:11471168.
28. Davidson, R. C.,, T. D. Moore,, A. R. Odom, and, J. Heitman. 2000. Characterization of the MFalpha pheromone of the human fungal pathogen Cryptococcus neoformans. Mol. Microbiol. 38:10171026.
29. Davidson, R. C.,, C. B. Nichols,, G. M. Cox,, J. R. Perfect, and, J. Heitman. 2003. A MAP kinase cascade composed of cell type specific and non-specific elements controls mating and differentiation of the fungal pathogen Cryptococcus neoformans. Mol. Microbiol. 49:469485.
30. Didsbury, J.,, R. F. Weber,, G. M. Bokoch,, T. Evans, and, R. Snyderman. 1989. rac, a novel ras-related family of proteins that are botulinum toxin substrates. J. Biol. Chem. 264:1637816382.
31. Dohlman, H. G. 2002. G proteins and pheromone signaling. Annu. Rev. Physiol. 64:129152.
32. Dohlman, H. G., and, J. W. Thorner. 2001. Regulation of G protein-initiated signal transduction in yeast: paradigms and principles. Annu. Rev. Biochem. 70:703754.
33. D’Souza, C. A.,, J. A. Alspaugh,, C. Yue,, T. Harashima,, G. M. Cox,, J. R. Perfect, and, J. Heitman. 2001. Cyclic AMP-dependent protein kinase controls virulence of the fungal pathogen Cryptococcus neoformans. Mol. Cell. Biol. 21:31793191.
34. Fraser, J. A.,, S. Diezmann,, R. L. Subaran,, A. Allen,, K. B. Lengeler,, F. S. Dietrich, and, J. Heitman. 2004. Convergent evolution of chromosomal sex-determining regions in the animal and fungal kingdoms. PLoS Biol. 2:e384.
35. Gilman, A. G. 1987. G-proteins: transducers of receptor-generated signals. Annu. Rev. Biochem. 56:615649.
36. Gold, S. E.,, S.M. Brogdon,, M.E. Mayorga, and, J. W. Kronstad. 1997. The Ustilago maydis regulatory subunit of a cAMP-dependent protein kinase is required for gall formation in maize. Plant Cell 9:15851594.
37. Hagen, D. C.,, G. McCaffrey, and, G. F. Sprague, Jr. 1986. Evidence the yeast STE3 gene encodes a receptor for the peptide pheromone a-factor: gene sequence and implications for the structure of the presumed receptor. Proc. Natl. Acad. Sci. USA 83:14181422.
38. Harashima, T., and, J. Heitman. 2002. The Galpha protein Gpa2 controls yeast differentiation by interacting with kelch repeat proteins that mimic Gbeta subunits. Mol. Cell 10:163173.
39. Harashima, T., and, J. Heitman. 2005. Galpha subunit Gpa2 recruits kelch repeat subunits that inhibit receptor-G protein coupling during cAMP-induced dimorphic transitions in Saccharomyces cerevisiae. Mol. Biol. Cell 16:45574571.
40. Hicks, J. K.,, Y.S. Bahn, and, J. Heitman. 2005. Pde1 phosphodiesterase modulates cyclic AMP levels through a protein kinase A-mediated negative feedback loop in Cryptococcus neoformans. Eukaryot. Cell 4:19711981.
41. Higgins, J. B., and, P. J. Casey. 1996. The role of prenylation in G-protein assembly and function. Cell. Signal. 8:433437.
42. Hoffman, C. S. 2007. Propping up our knowledge of G protein signaling pathways: diverse functions of putative non-canonical Gbeta subunits in fungi. Sci. STKE 2007:pe3.
43. Hsueh, Y. P., and, W. C. Shen. 2005. A homolog of Ste6, the a-factor transporter in Saccharomyces cerevisiae, is required for mating but not for monokaryotic fruiting in Cryptococcus neoformans. Eukaryot. Cell 4:147155.
44. Hsueh, Y. P.,, C. Xue, and, J. Heitman. 2007. G protein signaling governing cell fate decisions involves opposing Galpha subunits in Cryptococcus neoformans. Mol. Biol. Cell 18:32373249.
45. Hsueh, Y. P.,, C. Xue, and, J. Heitman. 2009. A constitutively active GPCR governs morphogenic transitions in Cryptococcus neoformans. EMBO J. 28:12201233.
46. Hurowitz, E. H.,, J. M. Melnyk,, Y. J. Chen,, H. Kouros-Mehr,, M. I. Simon, and, H. Shizuya. 2000. Genomic characterization of the human heterotrimeric G protein alpha, beta, and gamma subunit genes. DNA Res. 7:111120.
47. Ivey, F. D., and, C. S. Hoffman. 2002. Pseudostructural inhibitors of G protein signaling during development. Dev. Cell 3:154155.
48. Kozubowski, L.,, S.C. Lee, and, J. Heitman. 2009. Signalling pathways in the pathogenesis of Cryptococcus. Cell. Microbiol. 11:370380.
49. Kraakman, L.,, K. Lemaire,, P. Ma,, A. W. Teunissen,, M. C. Donaton,, P. Van Dijck,, J. Winderickx,, J. H. de Winde, and, J. M. Thevelein. 1999. A Saccharomyces cere-visiae G-protein coupled receptor, Gpr1, is specifically required for glucose activation of the cAMP pathway during the transition to growth on glucose. Mol. Microbiol. 32:10021012.
50. Kronstad, J. W., and, C. Staben. 1997. Mating type in filamentous fungi. Annu. Rev. Genet. 31:245276.
51. Kwon-Chung, K. J. 1976. Morphogenesis of Filobasidiella neoformans, the sexual state of Cryptococcus neoformans. Mycologia 68:821833.
52. Kwon-Chung, K. J., and, J. E. Bennett. 1978. Distribution of a and a mating types of Cryptococcus neoformans among natural and clinical isolates. Am. J. Epidemiol. 108:337340.
53. Kwon-Chung, K. J.,, J. C. Edman, and, B. L. Wickes. 1992. Genetic association of mating types and virulence in Cryptococcus neoformans. Infect. Immun. 60:602605.
54. Landry, S., and, C. S. Hoffman. 2001. The git5 Gβ and git11 Gγ form an atypical Gβy dimer acting in the fission yeast glucose/cAMP pathway. Genetics 157:11591168.
55. Landry, S.,, M. T Pettit,, E. Apolinario, and, C. S. Hoffman. 2000. The fission yeast git5 gene encodes a Gβ subunit required for glucose-triggered adenylate cyclase activation. Genetics 154:14631471.
56. Lemaire, K.,, S. Van de Velde,, P. Van Dijck, and, J. M. Thevelein. 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 16:293299.
57. Lengeler, K. B.,, D. S. Fox,, J. A. Fraser,, A. Allen,, K. Forrester,, F. S. Dietrich, and, J. Heitman. 2002. Mating-type locus of Cryptococcus neoformans: a step in the evolution of sex chromosomes. Eukaryot. Cell 1:704718.
58. Li, L.,, G. Shen,, Z. G. Zhang,, Y. L. Wang,, J. K. Thompson, and, P. Wang. 2007. Canonical heterotrimeric G proteins regulating mating and virulence of Cryptococcus neoformans. Mol. Biol. Cell 18:42014209.
59. Liebmann, B.,, M. Muller,, A. Braun, and, A. A. Brakhage. 2004. The cyclic AMP-dependent protein kinase A network regulates development and virulence in Aspergillus fumigatus. Infect. Immun. 72:51935203.
60. Liu, O. W.,, C.D. Chun,, E.D. Chow,, C. Chen,, H. D. Madhani, and, S. M. Noble. 2008. Systematic genetic analysis of virulence in the human fungal pathogen Cryptococcus neoformans. Cell 135:174188.
61. Lorenz, M. C., and, J. Heitman. 1997. Yeast pseudohyphal growth is regulated by GPA2, a G protein a homolog. EMBO J. 16:70087018.
62. Lorenz, M. C.,, X. Pan,, T. Harashima,, M. Cardenas,, Y. Xue,, J. P. Hirsch, and, J. Heitman. 2000. The G protein-coupled receptor Gpr1 is a nutrient sensor that regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Genetics 154:609622.
63. Ma, P.,, S. Wera,, P. Van Dijck, and, J. M. Thevelein. 1999. The PDE1-encoded low-affinity phosphodiesterase in the yeast Saccharomyces cerevisiae has a specific function in controlling agonist-induced cAMP signaling. Mol. Biol. Cell 10:91104.
64. Maidan, M. M.,, L. De Rop,, J. Serneels,, S. Exler,, S. Rupp,, H. Tournu,, J. M. Thevelein, and, P. Van Dijck. 2005. The G protein-coupled receptor Gpr1 and the Galpha protein Gpa2 act through the cAMP-protein kinase A pathway to induce morphogenesis in Candida albicans. Mol. Biol. Cell 16:19711986.
65. McClelland, C. M.,, J. Fu,, G. L. Woodlee,, T.S. Seymour, and, B. L. Wickes. 2002. Isolation and characterization of the Cryptococcus neoformans MATa pheromone gene. Genetics 160:935947.
66. Moore, T. D., and, J. C. Edman. 1993. The alpha-mating type locus of Cryptococcus neoformans contains a peptide pheromone gene. Mol. Cell. Biol. 13:19621970.
67. Mylonakis, E.,, F.M. Ausubel,, J.R. Perfect,, J. Heitman, and, S. B. Calderwood. 2002. Killing of Caenorhabditis elegans by Cryptococcus neoformans as a model of yeast pathogenesis. Proc. Natl. Acad. Sci. USA 99:1567515680.
68. Nichols, C. B.,, J. Ferreyra,, E. R. Ballou, and, J. A. Alspaugh. 2009. Subcellular localization directs signaling specificity of the Cryptococcus neoformans Ras1 protein. Eukaryot. Cell 8:181189.
69. Nichols, C. B.,, J.A. Fraser, and, J. Heitman. 2004. PAK kinases Ste20 and Pak1 govern cell polarity at different stages of mating in Cryptococcus neoformans. Mol. Biol. Cell 15:44764489.
70. Nichols, C. B.,, Z. Perfect, and, J. A. Alspaugh. 2007. A Ras1-Cdc24 signal transduction pathway mediates thermotolerance in the fungal pathogen Cryptococcus neoformans. Mol. Microbiol. 63:11181130.
71. Nielsen, K.,, G. M. Cox,, P. Wang,, D. L. Toffaletti,, J. R. Perfect, and, J. Heitman. 2003. Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates. Infect. Immun. 71:48314841.
72. Nielsen, K.,, R. E. Marra,, F. Hagen,, T. Boekhout,, T. G. Mitchell,, G. M. Cox, and, J. Heitman. 2005. Interaction between genetic background and the mating-type locus in Cryptococcus neoformans virulence potential. Genetics 171:975983.
73. Nielsen, O.,, J. Davey, and, R. Egel. 1992. The ras1 function of Schizosaccharomyces pombe mediates pheromone-induced transcprition. EMBO J. 11:13911395.
74. Nocero, M.,, T. Isshiki,, M. Yamamoto, and, C. S. Hoffman. 1994. Glucose repression of fbp1 transcription in Schizosaccharomyces pombe is partially regulated by adenylate cyclase activation by a G protein α subunit encoded by gpa2 (git8). Genetics 138:3945.
75. Palmer, D. A.,, J. K. Thompson,, L. Li,, A. Prat, and, P. Wang. 2006. Gib2, a novel Gbeta-like/RACK1 homolog, functions as a Gbeta subunit in cAMP signaling and is essential in Cryptococcus neoformans. J. Biol. Chem. 281:3259632605.
76. Peeters, T.,, W. Louwet,, R. Gelade,, D. Nauwelaers,, J. M. Thevelein, and, M. Versele. 2006. Kelch-repeat proteins interacting with the Galpha protein Gpa2 bypass adenylate cyclase for direct regulation of protein kinase A in yeast. Proc. Natl. Acad. Sci. USA 103:1303413039.
77. Pukkila-Worley, R., and, J. A. Alspaugh. 2004. Cyclic AMP signaling in Cryptococcus neoformans. FEMS Yeast Res. 4:361367.
78. Pukkila-Worley, R.,, Q.D. Gerrald,, P.R. Kraus,, M.J. Boily,, M. J Davis,, S. S. Giles,, G. M Cox,, J. Heitman, and, J. A. Alspaugh. 2005. Transcriptional network of multiple capsule and melanin genes governed by the Cryptococcus neoformans cyclic AMP cascade. Eukaryot. Cell 4:190201.
79. Rocha, C. R.,, K. Schroppel,, D. Harcus,, A. Marcil,, D. Dignard,, B. N. Taylor,, D. Y. Thomas,, M. Whiteway,, and E. Leberer. 2001. Signaling through adenylyl cyclase is essential for hyphal growth and virulence in the pathogenic fungus Candida albicans. Mol. Biol. Cell 12:36313643.
80. Rolland, F., J. Winderickx, and, J. M. Thevelein. 2002. Glucose-sensing and -signalling mechanisms in yeast. FEMS Yeast Res. 2:183201.
81. Shen, G.,, Y. L. Wang,, A. Whittington,, L. Li, and, P. Wang. 2008. The RGS protein Crg2 regulates pheromone and cyclic AMP signaling in Cryptococcus neoformans. Eukaryot. Cell 7:15401548.
82. Shen, W. C.,, R. C. Davidson,, G. M. Cox, and, J. Heitman. 2002. Pheromones stimulate mating and differentiation via paracrine and autocrine signaling in Cryptococcus neoformans. Eukaryot. Cell 1:366377.
83. Smrcka, A. V. 2008. G protein betagamma subunits: central mediators of G protein-coupled receptor signaling. Cell. Mol. Life Sci. 65:21912214.
84. Sternweis, P. C. 1994. The active role of βγ in signal transduction. Curr. Opin. Cell. Biol. 6:198203.
85. Toda, T.,, I. Uno,, T. Ishikawa,, S. Powers,, T. Kataoka,, D. Broek,, S. Cameron,, J. Broach,, K. Matsumoto, and, M. Wigler. 1985. In yeast, RAS proteins are controlling elements of adenylate cyclase. Cell 40:2736.
86. Vallim, M. A.,, C.B. Nichols,, L. Fernandes,, K. L. Cramer, and, J. A. Alspaugh. 2005. A Rac homolog functions downstream of Ras1 to control hyphal differentiation and high-temperature growth in the pathogenic fungus Cryptococcus neoformans. Eukaryot. Cell 4:10661078.
87. Wang, P.,, J. Cutler,, J. King, and, D. Palmer. 2004. Mutation of the regulator of G protein signaling Crg1 increases virulence in Cryptococcus neoformans. Eukaryot. Cell 3:10281035.
88. Wang, P.,, C. B. Nichols,, K. B. Lengeler,, M. E. Cardenas,, G. M. Cox,, J. R. Perfect, and, J. Heitman. 2002. Mating-type-specific and nonspecific PAK kinases play shared and divergent roles in Cryptococcus neoformans. Eukaryot. Cell 1:257272.
89. Wang, P.,, J.R. Perfect, and, J. Heitman. 2000. The G-protein beta subunit GPB1 is required for mating and haploid fruiting in Cryptococcus neoformans. Mol. Cell. Biol. 20:352362.
90. Waugh, M. S.,, C.B. Nichols,, C.M. DeCesare,, G. M Cox,, J. Heitman, and, J. A. Alspaugh. 2002. Ras1 and Ras2 contribute shared and unique roles in physiology and virulence of Cryptococcus neoformans. Microbiology 148:191201.
91. Waugh, M. S.,, M.A. Vallim,, J. Heitman, and, J. A. Alspaugh. 2003. Ras1 controls pheromone expression and response during mating in Cryptococcus neoformans. Fungal Genet. Biol. 38:110121.
92. Wickes, B. L.,, U. Edman, and, J. C. Edman. 1997. The Cryptococcus neoformans STE12alpha gene: a putative Saccharomyces cerevisiae STE12 homologue that is mating type specific. Mol. Microbiol. 26:951960.
93. Xue, C.,, Y. S. Bahn,, G.M. Cox, and, J. Heitman. 2006. G protein-coupled receptor Gpr4 senses amino acids and activates the cAMP-PKA pathway in Cryptococcus neoformans. Mol. Biol. Cell 17:667679.
94. Xue, C.,, Y. P. Hsueh,, L. Chen, and, J. Heitman. 2008. The RGS protein Crg2 regulates both pheromone and cAMP signalling in Cryptococcus neoformans. Mol. Microbiol. 70:379395.
95. Xue, C.,, Y.P. Hsueh, and, J. Heitman. 2008. Magnificent seven: roles of G protein-coupled receptors in extracellular sensing in fungi. FEMS Microbiol. Rev. 32:10101032.
96. Xue, Y.,, M. Batlle, and, J. P. Hirsch. 1998. GPR1 encodes a putative G protein-coupled receptor that associates with the Gpa2p Gα subunit and functions in a Ras-independent pathway. EMBO J. 17:19962007.
97. Yue, C.,, L. M. Cavallo,, J. A. Alspaugh,, P. Wang,, G. M. Cox,, J. R. Perfect, and, J. Heitman. 1999. The STE12alpha homolog is required for haploid filamentation but largely dispensable for mating and virulence in Cryptococcus neoformans. Genetics 153:16011615.
98. Zeller, C. E., S. C. Parnell, and, H. G. Dohlman. 2007. The RACK1 ortholog Asc1 functions as a G-protein beta subunit coupled to glucose responsiveness in yeast. J. Biol. Chem. 282:2516825176.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error