Program in Molecular Medicine
Cell Biology | Developmental Biology
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.
Immune synapse, Rab8, TCR recycling
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DOI of Published Version
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
Journal of cell science
Finetti F, Patrussi L, Galgano D, Cassioli C, Perinetti G, Pazour GJ, Baldari CT. (2015). The small GTPase Rab8 interacts with VAMP-3 to regulate the delivery of recycling T-cell receptors to the immune synapse. Open Access Publications by UMMS Authors. https://doi.org/10.1242/jcs.171652. Retrieved from https://escholarship.umassmed.edu/oapubs/2692