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VAMP7 controls T cell activation by regulating the recruitment and phosphorylation of vesicular Lat at TCR-activation sites

机译:VAMP7通过调节TCR激活位点囊泡Lat的募集和磷酸化来控制T细胞激活

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摘要

The mechanisms by which Lat (a key adaptor in the T cell antigen receptor (TCR) signaling pathway) and the TCR come together after TCR triggering are not well understood. We investigate here the role of SNARE proteins, which are part of protein complexes involved in the docking, priming and fusion of vesicles with opposing membranes, in this process. Here we found, by silencing approaches and genetically modified mice, that the vesicular SNARE VAMP7 was required for the recruitment of Lat-containing vesicles to TCR-activation sites. Our results indicated that this did not involve fusion of Lat-containing vesicles with the plasma membrane. VAMP7, which localized together with Lat on the subsynaptic vesicles, controlled the phosphorylation of Lat, formation of the TCR-Lat-signaling complex and, ultimately, activation of T cells. Our findings suggest that the transport and docking of Lat-containing vesicles with target membranes containing TCRs regulates TCR-induced signaling.
机译:TCR触发后,Lat(T细胞抗原受体(TCR)信号传导途径中的关键衔接子)与TCR结合在一起的机制尚不清楚。我们在这里研究了SNARE蛋白的作用,SNARE蛋白是蛋白质复合物的一部分,在此过程中涉及与相对膜的对接,引发和融合。在这里,我们发现,通过沉默方法和转基因小鼠,囊泡SNARE VAMP7是将含Lat囊泡募集到TCR激活位点所必需的。我们的结果表明,这不涉及含Lat的囊泡与质膜的融合。与Lat一起位于突触下小泡上的VAMP7控制Lat的磷酸化,TCR-Lat信号复合物的形成,并最终激活T细胞。我们的发现表明,含Lat的囊泡与含有TCR的靶膜的转运和对接调节了TCR诱导的信号传导。

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