| Literature DB >> 22308290 |
Geneviève de Saint Basile1,2,3,4, Gaël Ménasché1,2,3, Mathieu Kurowska1,2,3, Nicolas Goudin2,3, Nadine T Nehme1,2,3, Magali Court5,6,7, Jérôme Garin5,6,7, Alain Fischer1,2,3,4.
Abstract
Cytotoxic T lymphocytes kill target cells via the polarized secretion of cytotoxic granules at the immune synapse. The lytic granules are initially recruited around the polarized microtubule-organizing center. In a dynein-dependent transport process, the granules move along microtubules toward the microtubule-organizing center in the minus-end direction. Here, we found that a kinesin-1-dependent process is required for terminal transport and secretion of polarized lytic granule to the immune synapse. We show that synaptotagmin-like protein 3 (Slp3) is an effector of Rab27a in cytotoxic T lymphocytes and interacts with kinesin-1 through the tetratricopeptide repeat of the kinesin-1 light chain. Inhibition of the Rab27a/Slp3/kinesin-1 transport complex impairs lytic granule secretion. Our data provide further molecular insights into the key functional and regulatory mechanisms underlying the terminal transport of cytotoxic granules and the latter's secretion at the immune synapse.Entities:
Mesh：
Substances：
Year: 2012 PMID： 22308290 PMCID： PMC3824283 DOI： 10.1182/blood-2011-09-382556
Source DB: PubMed Journal: Blood ISSN： 0006-4971 Impact factor: 22.113