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- Title
Secretory cytotoxic granule maturation and exocytosis require the effector protein hMunc13-4.
- Authors
Ménager, Mickaël M; Ménasché, Gaël; Romao, Maryse; Knapnougel, Perrine; Ho, Chen-Hsuan; Garfa, Mériem; Raposo, Graça; Feldmann, Jérôme; Fischer, Alain; de Saint Basile, Geneviève
- 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.
- Publication
Nature immunology, 2007, Vol 8, Issue 3, p257
- ISSN
1529-2908
- Publication type
Journal Article
- DOI
10.1038/ni1431