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Secretory cytotoxic granule maturation and exocytosis require the effector protein hMunc13-4

Abstract : Cytotoxic T lymphocytes and natural killer cells exert their cytotoxic activity through the polarized secretion of cytotoxic granules at the immunological synapse. Rab27a and hMunc13-4 are critical effectors of the exocytosis of cytotoxic granules. Here we show that the cytotoxic function of lymphocytes requires the cooperation of two types of organelles: the lysosomal cytotoxic granule and the endosomal 'exocytic vesicle'. Independently of Rab27a, hMunc13-4 mediated the assembly of Rab11(+) recycling and Rab27(+) late endosomal vesicles, constituting a pool of vesicles destined for regulated exocytosis. It also primed cytotoxic granule fusion, possibly through interaction with active Rab27a. Cytotoxic T lymphocyte-target cell recognition induced rapid polarization of both types of organelles, which coalesced near the cell-cell contact area. Our data provide insight into the regulation of the generation and release of cytotoxic granules by effector cytotoxic T lymphocytes and natural killer cells.
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Contributor : Gaël Ménasché Connect in order to contact the contributor
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Mickaël Ménager, Gaël Ménasché, Maryse Romao, Perrine Knapnougel, Chen-Hsuan Ho, et al.. Secretory cytotoxic granule maturation and exocytosis require the effector protein hMunc13-4. Nature Immunology, Nature Publishing Group, 2007, 8 (3), pp.257-267. ⟨10.1038/ni1431⟩. ⟨inserm-02440339⟩



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