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Secretion from Myeloid Cells: Secretory Lysosomes

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  • Author: Gillian M. Griffiths1
  • Editor: Siamon Gordon2
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Cambridge CB2 0XY, United Kingdom; 2: Oxford University, Oxford, United Kingdom
    • Source: microbiolspec July 2016 vol. 4 no. 4 doi:10.1128/microbiolspec.MCHD-0030-2016
  • Received 03 March 2016 Accepted 15 March 2016 Published 29 July 2016
  • Gillian M. Griffiths, [email protected]
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  • Abstract:

    Many cells of the myeloid lineage use an unusual secretory organelle to deliver their effector mechanisms. In these cells, the lysosomal compartment is often modified not only to fulfill the degradative functions of a lysosome but also as a mechanism for secreting additional proteins that are found in the lysosomes of each specialized cell type. These extra proteins vary from one cell type to another according to the specialized function of the cell. For example, mast cells package histamine; cytotoxic T cells express perforin; azurophilic granules in neutrophils express antimicrobial peptides, and platelets von Willebrand factor. Upon release, these very different proteins can trigger inflammation, cell lysis, microbial death, and clotting, respectively, and hence deliver the very different effector mechanisms of these different myeloid cells.

  • Citation: Griffiths G. 2016. Secretion from Myeloid Cells: Secretory Lysosomes. Microbiol Spectrum 4(4):MCHD-0030-2016. doi:10.1128/microbiolspec.MCHD-0030-2016.

Key Concept Ranking

Plasma Membrane
0.800855
Cytotoxic T Cell
0.48869997
Golgi Apparatus
0.45726317
Proteins
0.44610295
Mast Cells
0.42944068
0.800855

References

1. Blott EJ, Griffiths GM. 2002. Secretory lysosomes. Nat Rev Mol Cell Biol 3:122–131. [PubMed][CrossRef]
2. Griffiths G. 2002. What’s special about secretory lysosomes? Semin Cell Dev Biol 13:279–284. [PubMed][CrossRef]
3. Stepp SE, Dufourcq-Lagelouse R, Le Deist F, Bhawan S, Certain S, Mathew PA, Henter JI, Bennett M, Fischer A, de Saint Basile G, Kumar V. 1999. Perforin gene defects in familial hemophagocytic lymphohistiocytosis. Science 286:1957–1959. [PubMed][CrossRef]
4. Luzio JP, Hackmann Y, Dieckmann NM, Griffiths GM. 2014. The biogenesis of lysosomes and lysosome-related organelles. Cold Spring Harb Perspect Biol 6:a016840. doi:10.1101/cshperspect.a016840. [PubMed][CrossRef]
5. Fukuda M. 2013. Rab27 effectors, pleiotropic regulators in secretory pathways. Traffic 14:949–963. [PubMed][CrossRef]
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12. Holt O, Kanno E, Bossi G, Booth S, Daniele T, Santoro A, Arico M, Saegusa C, Fukuda M, Griffiths GM. 2008. Slp1 and Slp2-a localize to the plasma membrane of CTL and contribute to secretion from the immunological synapse. Traffic 9:446–457. [PubMed][CrossRef]
13. Kurowska M, Goudin N, Nehme NT, Court M, Garin J, Fischer A, de Saint Basile G, Ménasché G. 2012. Terminal transport of lytic granules to the immune synapse is mediated by the kinesin-1/Slp3/Rab27a complex. Blood 119:3879–3889. [PubMed][CrossRef]
14. Stinchcombe JC, Griffiths GM. 2007. Secretory mechanisms in cell-mediated cytotoxicity. Annu Rev Cell Dev Biol 23:495–517. [PubMed][CrossRef]
15. Griffiths GM, Tsun A, Stinchcombe JC. 2010. The immunological synapse: a focal point for endocytosis and exocytosis. J Cell Biol 189:399–406. [PubMed][CrossRef]
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17. Singla V, Reiter JF. 2006. The primary cilium as the cell’s antenna: signaling at a sensory organelle. Science 313:629–633. [PubMed][CrossRef]
18. Finetti F, Paccani SR, Riparbelli MG, Giacomello E, Perinetti G, Pazour GJ, Rosenbaum JL, Baldari CT. 2009. Intraflagellar transport is required for polarized recycling of the TCR/CD3 complex to the immune synapse. Nat Cell Biol 11:1332–1339. [PubMed][CrossRef]
19. de la Roche M, Ritter AT, Angus KL, Dinsmore C, Earnshaw CH, Reiter JF, Griffiths GM. 2013. Hedgehog signaling controls T cell killing at the immunological synapse. Science 342:1247–1250. [PubMed][CrossRef]
20. Tsun A, Qureshi I, Stinchcombe JC, Jenkins MR, de la Roche M, Kleczkowska J, Zamoyska R, Griffiths GM. 2011. Centrosome docking at the immunological synapse is controlled by Lck signaling. J Cell Biol 192:663–674. [PubMed][CrossRef]
21. Jenkins MR, Tsun A, Stinchcombe JC, Griffiths GM. 2009. The strength of T cell receptor signal controls the polarization of cytotoxic machinery to the immunological synapse. Immunity 31:621–631. [PubMed][CrossRef]
22. Zhao F, Cannons JL, Dutta M, Griffiths GM, Schwartzberg PL. 2012. Positive and negative signaling through SLAM receptors regulate synapse organization and thresholds of cytolysis. Immunity 36:1003–1016. [PubMed][CrossRef]
23. Pulecio J, Petrovic J, Prete F, Chiaruttini G, Lennon-Dumenil AM, Desdouets C, Gasman S, Burrone OR, Benvenuti F. 2010. Cdc42-mediated MTOC polarization in dendritic cells controls targeted delivery of cytokines at the immune synapse. J Exp Med 207:2719–2732. [PubMed][CrossRef]
24. Yuseff MI, Reversat A, Lankar D, Diaz J, Fanget I, Pierobon P, Randrian V, Larochette N, Vascotto F, Desdouets C, Jauffred B, Bellaiche Y, Gasman S, Darchen F, Desnos C, Lennon-Duménil AM. 2011. Polarized secretion of lysosomes at the B cell synapse couples antigen extraction to processing and presentation. Immunity 35:361–374. [PubMed][CrossRef]
25. Stinchcombe JC, Salio M, Cerundolo V, Pende D, Arico M, Griffiths GM. 2011. Centriole polarisation to the immunological synapse directs secretion from cytolytic cells of both the innate and adaptive immune systems. BMC Biol 9:45. doi:10.1186/1741-7007-9-45. [CrossRef]
26. Joulia R, Gaudenzio N, Rodrigues M, Lopez J, Blanchard N, Valitutti S, Espinosa E. 2015. Mast cells form antibody-dependent degranulatory synapse for dedicated secretion and defence. Nat Commun 6:6174. doi:10.1038/ncomms7174. [PubMed][CrossRef]
27. Gaudenzio N, Espagnolle N, Mars LT, Liblau R, Valitutti S, Espinosa E. 2009. Cell-cell cooperation at the T helper cell/mast cell immunological synapse. Blood 114:4979–4988. [PubMed][CrossRef]
28. Tapper H, Furuya W, Grinstein S. 2002. Localized exocytosis of primary (lysosomal) granules during phagocytosis: role of Ca 2+-dependent tyrosine phosphorylation and microtubules. J Immunol 168:5287–5296. [PubMed][CrossRef]
29. Scott CC, Dobson W, Botelho RJ, Coady-Osberg N, Chavrier P, Knecht DA, Heath C, Stahl P, Grinstein S. 2005. Phosphatidylinositol-4,5-bisphosphate hydrolysis directs actin remodeling during phagocytosis. J Cell Biol 169:139–149. [PubMed][CrossRef]
30. Catz SD. 2014. The role of Rab27a in the regulation of neutrophil function. Cell Microbiol 16:1301–1310. [PubMed][CrossRef]
31. Hackmann Y, Graham SC, Ehl S, Höning S, Lehmberg K, Aricò M, Owen DJ, Griffiths GM. 2013. Syntaxin binding mechanism and disease-causing mutations in Munc18-2. Proc Natl Acad Sci U S A 110:E4482–E4491. [PubMed][CrossRef]
32. Bin NR, Jung CH, Piggott C, Sugita S. 2013. Crucial role of the hydrophobic pocket region of Munc18 protein in mast cell degranulation. Proc Natl Acad Sci U S A 110:4610–4615. [PubMed][CrossRef]
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/content/journal/microbiolspec/10.1128/microbiolspec.MCHD-0030-2016
2016-07-29
2019-10-20

Abstract:

Many cells of the myeloid lineage use an unusual secretory organelle to deliver their effector mechanisms. In these cells, the lysosomal compartment is often modified not only to fulfill the degradative functions of a lysosome but also as a mechanism for secreting additional proteins that are found in the lysosomes of each specialized cell type. These extra proteins vary from one cell type to another according to the specialized function of the cell. For example, mast cells package histamine; cytotoxic T cells express perforin; azurophilic granules in neutrophils express antimicrobial peptides, and platelets von Willebrand factor. Upon release, these very different proteins can trigger inflammation, cell lysis, microbial death, and clotting, respectively, and hence deliver the very different effector mechanisms of these different myeloid cells.

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Secretion from Myeloid Cells: Secretory Lysosomes
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Citation: Griffiths G. 2016. Secretion from myeloid cells: secretory lysosomes. microbiolspec 4(4): doi:10.1128/microbiolspec.MCHD-0030-2016
/content/microbiolspec/10.1128/microbiolspec.MCHD-0030-2016.fig1
FIGURE 1

Rab27a interacts with different effector proteins to provide different modes of secretion. (Left) In melanosomes, Rab27a interacts with the Slp melanophilin (Mlph), which in turn interacts with myosin (Myo) Va and captures melanosomes onto cortical actin at the plus ends of microtubules. (Right) In CTLs, Rab27a interacts with Munc13-4 on secretory lysosomes and also interacts with Slp1 to -3, which are localized to the plasma membrane.

microbiolspec/4/4/MCHD-0030-2016-fig1_thmb.gif
microbiolspec/4/4/MCHD-0030-2016-fig1.gif
Image of FIGURE 1

Click to view

FIGURE 1

Rab27a interacts with different effector proteins to provide different modes of secretion. (Left) In melanosomes, Rab27a interacts with the Slp melanophilin (Mlph), which in turn interacts with myosin (Myo) Va and captures melanosomes onto cortical actin at the plus ends of microtubules. (Right) In CTLs, Rab27a interacts with Munc13-4 on secretory lysosomes and also interacts with Slp1 to -3, which are localized to the plasma membrane.

Source: microbiolspec July 2016 vol. 4 no. 4 doi:10.1128/microbiolspec.MCHD-0030-2016
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/content/microbiolspec/10.1128/microbiolspec.MCHD-0030-2016.fig2
FIGURE 2

Secretory lysosomes are delivered to an area of plasma membrane depleted in cortical actin. CTLs expressing actin-green fluorescent protein (green), fixed and stained with CD63 (red), forming a synapse viewed from the side and en face. Reprinted from reference ( 11 ), with permission.

microbiolspec/4/4/MCHD-0030-2016-fig2_thmb.gif
microbiolspec/4/4/MCHD-0030-2016-fig2.gif
Image of FIGURE 2

Click to view

FIGURE 2

Secretory lysosomes are delivered to an area of plasma membrane depleted in cortical actin. CTLs expressing actin-green fluorescent protein (green), fixed and stained with CD63 (red), forming a synapse viewed from the side and en face. Reprinted from reference ( 11 ), with permission.

Source: microbiolspec July 2016 vol. 4 no. 4 doi:10.1128/microbiolspec.MCHD-0030-2016
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Download as Powerpoint
/content/microbiolspec/10.1128/microbiolspec.MCHD-0030-2016.fig3
FIGURE 3

Naive CD8 T cells express only low levels of Rac1 and no secretory lysosomes, Upon activation, TCR signaling triggers secretory lysosome biogenesis and prearms the CTL to kill. TCR signaling also activates Hh signaling, increasing levels of Rac1, required for actin reorganization and microtubule organization and thereby secretory lysosome polarization and release.

microbiolspec/4/4/MCHD-0030-2016-fig3_thmb.gif
microbiolspec/4/4/MCHD-0030-2016-fig3.gif
Image of FIGURE 3

Click to view

FIGURE 3

Naive CD8 T cells express only low levels of Rac1 and no secretory lysosomes, Upon activation, TCR signaling triggers secretory lysosome biogenesis and prearms the CTL to kill. TCR signaling also activates Hh signaling, increasing levels of Rac1, required for actin reorganization and microtubule organization and thereby secretory lysosome polarization and release.

Source: microbiolspec July 2016 vol. 4 no. 4 doi:10.1128/microbiolspec.MCHD-0030-2016
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Download as Powerpoint

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