Servicio de Inmunología, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Instituto Investigación Sanitaria Princesa (IIS-IP), Madrid, Spain.
EMBO J. 2012 Nov 5;31(21):4140-52. doi: 10.1038/emboj.2012.242. Epub 2012 Aug 24.
The role of microtubules (MTs) in the control and dynamics of the immune synapse (IS) remains unresolved. Here, we show that T cell activation requires the growth of MTs mediated by the plus-end specific protein end-binding 1 (EB1). A direct interaction of the T cell receptor (TCR) complex with EB1 provides the molecular basis for EB1 activity promoting TCR encounter with signalling vesicles at the IS. EB1 knockdown alters TCR dynamics at the IS and prevents propagation of the TCR activation signal to LAT, thus inhibiting activation of PLCγ1 and its localization to the IS. These results identify a role for EB1 interaction with the TCR in controlling TCR sorting and its connection with the LAT/PLCγ1 signalosome.
微管(MTs)在免疫突触(IS)的控制和动态中所扮演的角色仍未得到解决。在这里,我们表明 T 细胞的激活需要由末端结合蛋白 1(EB1)介导的 MT 生长。T 细胞受体(TCR)复合物与 EB1 的直接相互作用为 EB1 活性促进 TCR 在 IS 与信号小泡相遇提供了分子基础。EB1 的敲低会改变 TCR 在 IS 上的动力学,并阻止 TCR 激活信号向 LAT 的传播,从而抑制 PLCγ1 的激活及其向 IS 的定位。这些结果确定了 EB1 与 TCR 的相互作用在控制 TCR 分拣及其与 LAT/PLCγ1 信号体连接中的作用。