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Centrosome polarization delivers secretory granules to the immunological synapse

Stinchcombe, Jane C., Majorovits, Endre, Bossi, Giovanna, Fuller, Stephen, Griffiths, Gillian M.·2006·Nature

Abstract

Cytotoxic T lymphocytes (CTLs) destroy virally infected and tumorigenic cells by releasing the contents of specialized secretory lysosomes--termed 'lytic granules'--at the immunological synapse formed between the CTL and the target. On contact with the target cell, the microtubule organizing centre of the CTL polarizes towards the target and granules move along microtubules in a minus-end direction towards the polarized microtubule organizing centre. However, the final steps of secretion have remained unclear. Here we show that CTLs do not require actin or plus-end microtubule motors for secretion, but instead the centrosome moves to and contacts the plasma membrane at the central supramolecular activation cluster of the immunological synapse. Actin and IQGAP1 are cleared away from the synapse, and granules are delivered directly to the plasma membrane. These data show that CTLs use a previously unreported mechanism for delivering secretory granules to the immunological synapse, with granule secretion controlled by centrosome delivery to the plasma membrane.

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Crossref · 10.1038/nature05071

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  • Lysosome retrograde transport toward the immunological synapse is essential for natural killer and cytotoxic T lymphocyte killing of pathogen-infected cells.

    “Lysosome retrograde transport toward the immunological synapse is essential for the ability of natural killer and cytotoxic T lymphocytes to kill pathogen infected cells15”

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Research works printed but not linked: 23

  1. Stinchcombe, J., Bossi, G. & Griffiths, G. M. Linking albinism and immunity: the secrets of secretory lysosomes. Science 305, 55–59 (2004) · DOI
  2. Geiger, B., Rosen, D. & Berke, G. Spatial relationships of microtubule-organizing centers and the contact area of cytotoxic T lymphocytes and target cells. J. Cell Biol. 95, 137–143 (1982) · DOI
  3. Kupfer, A. & Dennert, G. Reorientation of the microtubule-organizing center and the Golgi apparatus in cloned cytotoxic lymphocytes triggered by binding to lysable target cells. J. Immunol. 133, 2762–2766 (1984) · DOI
  4. Stinchcombe, J. C., Bossi, G., Booth, S. & Griffiths, G. M. The immunological synapse of CTL contains a secretory domain and membrane bridges. Immunity 15, 751–761 (2001) · DOI
  5. Monks, C. R., Freiberg, B. A., Kupfer, H., Sciaky, N. & Kupfer, A. Three-dimensional segregation of supramolecular activation clusters in T cells. Nature 395, 82–86 (1998) · DOI
  6. Lin, J., Miller, M. J. & Shaw, A. S. The c-SMAC: sorting it all out (or in). J. Cell Biol. 170, 177–182 (2005) · DOI
  7. Kuhn, J. R. & Poenie, M. Dynamic polarization of the microtubule cytoskeleton during CTL-mediated killing. Immunity 16, 111–121 (2002) · DOI
  8. Poenie, M., Kuhn, J. & Combs, J. Real-time visualization of the cytoskeleton and effector functions in T cells. Curr. Opin. Immunol. 16, 428–438 (2004) · DOI
  9. Jordens, I., Marsman, M., Kuijl, C. & Neefjes, J. Rab proteins, connecting transport and vesicle fusion. Traffic 6, 1070–1077 (2005) · DOI
  10. Jordens, I. et al. The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein–dynactin motors. Curr. Biol. 11, 1680–1685 (2001) · DOI · Paper page
  11. Allan, V. J., Thompson, H. M. & McNiven, M. A. Motoring around the Golgi. Nature Cell Biol. 4, E236–E242 (2002) · DOI
  12. Cannon, J. L. & Burkhardt, J. K. The regulation of actin remodeling during T-cell–APC conjugate formation. Immunol. Rev. 186, 90–99 (2002) · DOI
  13. Stowers, L., Yelon, D., Berg, L. J. & Chant, J. Regulation of the polarization of T cells toward antigen-presenting cells by Ras-related GTPase CDC42. Proc. Natl Acad. Sci. USA 92, 5027–5031 (1995) · DOI
  14. Fukata, M. et al. Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170. Cell 109, 873–885 (2002) · DOI
  15. Lansbergen, G. & Akhmanova, A. Microtubule plus end: a hub of cellular activities. Traffic 7, 499–507 (2006) · DOI
  16. Piel, M., Nordberg, J., Euteneuer, U. & Bornens, M. Centrosome-dependent exit of cytokinesis in animal cells. Science 291, 1550–1553 (2001) · DOI · Paper page
  17. Gromley, A. et al. Centriolin anchoring of exocyst and SNARE complexes at the midbody is required for secretory-vesicle-mediated abscission. Cell 123, 75–87 (2005) · DOI
  18. Cowan, C. R. & Hyman, A. A. Centrosomes direct cell polarity independently of microtubule assembly in C. elegans embryos. Nature 431, 92–96 (2004) · DOI
  19. Sorokin, S. P. Reconstructions of centriole formation and ciliogenesis in mammalian lungs. J. Cell Sci. 3, 207–230 (1968) · DOI · Paper page
  20. Bornens, M. Centrosome composition and microtubule anchoring mechanisms. Curr. Opin. Cell Biol. 14, 25–34 (2002) · DOI
  21. Lange, B. M. & Gull, K. A molecular marker for centriole maturation in the mammalian cell cycle. J. Cell Biol. 130, 919–927 (1995) · DOI
  22. Ishikawa, H., Kubo, A., Tsukita, S. & Tsukita, S. Odf2-deficient mother centrioles lack distal/subdistal appendages and the ability to generate primary cilia. Nature Cell Biol. 7, 517–524 (2005) · DOI
  23. Fruth, U. et al. A novel serine proteinase (HuTSP) isolated from a cloned human CD8+ cytolytic T-cell line is expressed and secreted by activated CD4+ and CD8+ lymphocytes. Eur. J. Immunol. 17, 1625–1633 (1987) · DOI

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Metadata

Authors
Stinchcombe, J. C., Majorovits, E., Bossi, G., Fuller, S., & Griffiths, G. M.
Venue
Nature
Published
2006-09-28
Volume
443
Issue
7110
Pages
462-465
ISSN
  • 0028-0836
  • 1476-4687
Cited by
599
References
0
Language
en
Update notices
erratum (2006-11-09)

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