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.
journal_name
Bloodjournal_title
Bloodauthors
Kurowska M,Goudin N,Nehme NT,Court M,Garin J,Fischer A,de Saint Basile G,Ménasché Gdoi
10.1182/blood-2011-09-382556subject
Has Abstractpub_date
2012-04-26 00:00:00pages
3879-89issue
17eissn
0006-4971issn
1528-0020journal_volume
119pub_type
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