Tethering of vesicles to the Golgi by GMAP210 controls LAT delivery to the immune synapse

Andres Ernesto Zucchetti,Cosima T Baldari,Rosa M Rios,Gregory J Pazour,Stéphanie Dogniaux,Claire Hivroz,Jean-Marie Carpier,Mabel San Roman-Jouve,Michael W Stuck,Mathieu Maurin,Laurence Bataille

doi:10.1038/s41467-019-10891-w

Abstract

The T cell immune synapse is a site of intense vesicular trafficking. Here we show that the golgin GMAP210, known to capture vesicles and organize membrane traffic at the Golgi, is involved in the vesicular transport of LAT to the immune synapse. Upon activation, more GMAP210 interact with LAT-containing vesicles and go together with LAT to the immune synapse. Regulating LAT recruitment and LAT-dependent signaling, GMAP210 controls T cell activation. Using a rerouting and capture assay, we show that GMAP210 captures VAMP7-decorated vesicles. Overexpressing different domains of GMAP210, we also show that GMAP210 allows their specific delivery to the immune synapse by tethering LAT-vesicles to the Golgi. Finally, in a model of ectopic expression of LAT in ciliated cells, we show that GMAP210 tethering activity controls the delivery of LAT to the cilium. Hence, our results reveal a function for the golgin GMAP210 conveying specific vesicles to the immune synapse.

Highlights

The T cell immune synapse is a site of intense vesicular trafficking
We identify the golgin GMAP210 as a specific binder of vesicles containing LAT/VAMP7. We show that it controls the polarized recruitment of LAT at the immune synapse, the formation of the LAT signalosome, and the TCR-induced activation of T lymphocytes
We have previously shown that LAT is present in vesicles that are recruited to the immune synapse[13]

Summary

Introduction

We show that the golgin GMAP210, known to capture vesicles and organize membrane traffic at the Golgi, is involved in the vesicular transport of LAT to the immune synapse. We recently found that the plasma membrane pool of LAT, after its TCR-induced internalization, is following the canonical retrograde Rab6/syntaxin 16 pathway to the Golgi before being transported back to the immune synapse[24] This retrograde vesicular trafficking of LAT controls the formation of signaling complexes[13,24,25], known as signalosomes and regulates some aspects of T cell activation. It has been shown to bind the intraflagellar protein IFT2035,36 and controls trafficking of some cargos to the primary cilium and signaling by this structure[35,37,38]

Methods

Results

Conclusion