UMMS Affiliation

Program in Molecular Medicine

Date

7-15-2015

Document Type

Article

Disciplines

Cell Biology | Developmental Biology

Abstract

IFT20, a component of the intraflagellar transport (IFT) system that controls ciliogenesis, regulates immune synapse assembly in the non-ciliated T-cell by promoting T-cell receptor (TCR) recycling. Here, we have addressed the role of Rab8 (for which there are two isoforms Rab8a and Rab8b), a small GTPase implicated in ciliogenesis, in TCR traffic to the immune synapse. We show that Rab8, which colocalizes with IFT20 in Rab11(+) endosomes, is required for TCR recycling. Interestingly, as opposed to in IFT20-deficient T-cells, TCR(+) endosomes polarized normally beneath the immune synapse membrane in the presence of dominant-negative Rab8, but were unable to undergo the final docking or fusion step. This could be accounted for by the inability of the vesicular (v)-SNARE VAMP-3 to cluster at the immune synapse in the absence of functional Rab8, which is responsible for its recruitment. Of note, and similar to in T-cells, VAMP-3 interacts with Rab8 at the base of the cilium in NIH-3T3 cells, where it regulates ciliary growth and targeting of the protein smoothened. The results identify Rab8 as a new player in vesicular traffic to the immune synapse and provide insight into the pathways co-opted by different cell types for immune synapse assembly and ciliogenesis.

Rights and Permissions

Citation: J Cell Sci. 2015 Jul 15;128(14):2541-52. doi: 10.1242/jcs.171652. Epub 2015 Jun 1. Link to article on publisher's site

DOI of Published Version

10.1242/jcs.171652

Comments

Publisher PDF posted after 12 months as allowed by the publisher's author rights policy at http://jcs.biologists.org/content/rights-permissions.

Related Resources

Link to Article in PubMed

Keywords

Immune synapse, Rab8, TCR recycling

Journal Title

Journal of cell science

PubMed ID

26034069

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