Terminal transport of lytic granules to the immune synapse is mediated by the kinesin-1/Slp3/Rab27a complex.

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

Blood

journal_title

Blood

authors

Kurowska M,Goudin N,Nehme NT,Court M,Garin J,Fischer A,de Saint Basile G,Ménasché G

doi

10.1182/blood-2011-09-382556

subject

Has Abstract

pub_date

2012-04-26 00:00:00

pages

3879-89

issue

17

eissn

0006-4971

issn

1528-0020

journal_volume

119

pub_type

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