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- Title
Adaptor protein 3-dependent microtubule-mediated movement of lytic granules to the immunological synapse.
- Authors
Clark, Richard H; Stinchcombe, Jane C; Day, Anna; Blott, Emma; Booth, Sarah; Bossi, Giovanna; Hamblin, Terry; Davies, E Graham; Griffiths, Gillian M
- Abstract
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disease characterized by platelet defects and oculocutaneous albinism. Individuals with HPS type 2 (HPS2) lack the cytosolic adaptor protein 3 (AP-3) involved in lysosomal sorting, and are also immunodeficient. Here we characterize an HPS2 mutation and demonstrate that AP-3 deficiency leads to a loss of cytotoxic T lymphocyte (CTL)-mediated cytotoxicity. Although the lysosomal protein CD63 was mislocalized to the plasma membrane, perforin and granzymes were correctly localized to the lytic granules in AP-3-deficient CTLs. However, the lytic granules of AP-3-deficient CTLs were enlarged and were unable to move along microtubules and dock within the secretory domain of the immunological synapse. These data show that AP-3 is essential for polarized secretion from CTLs.
- Publication
Nature immunology, 2003, Vol 4, Issue 11, p1111
- ISSN
1529-2908
- Publication type
Journal Article
- DOI
10.1038/ni1000