Bouchet Jérôme, Del Río-Iñiguez Iratxe, Lasserre Rémi, Agüera-Gonzalez Sonia, Cuche Céline, Danckaert Anne, McCaffrey Mary W, Di Bartolo Vincenzo, Alcover Andrés
Lymphocyte Cell Biology Unit, Department of Immunology, Institut Pasteur, Paris, France CNRS URA 1961, Paris, France INSERM U1221, Paris, France
Lymphocyte Cell Biology Unit, Department of Immunology, Institut Pasteur, Paris, France CNRS URA 1961, Paris, France INSERM U1221, Paris, France.
EMBO J. 2016 Jun 1;35(11):1160-74. doi: 10.15252/embj.201593274. Epub 2016 May 6.
The immunological synapse generation and function is the result of a T-cell polarization process that depends on the orchestrated action of the actin and microtubule cytoskeleton and of intracellular vesicle traffic. However, how these events are coordinated is ill defined. Since Rab and Rho families of GTPases control intracellular vesicle traffic and cytoskeleton reorganization, respectively, we investigated their possible interplay. We show here that a significant fraction of Rac1 is associated with Rab11-positive recycling endosomes. Moreover, the Rab11 effector FIP3 controls Rac1 intracellular localization and Rac1 targeting to the immunological synapse. FIP3 regulates, in a Rac1-dependent manner, key morphological events, like T-cell spreading and synapse symmetry. Finally, Rab11-/FIP3-mediated regulation is necessary for T-cell activation leading to cytokine production. Therefore, Rac1 endosomal traffic is key to regulate T-cell activation.
免疫突触的生成和功能是T细胞极化过程的结果，该过程依赖于肌动蛋白和微管细胞骨架以及细胞内囊泡运输的协同作用。然而，这些事件如何协调尚不清楚。由于GTP酶的Rab和Rho家族分别控制细胞内囊泡运输和细胞骨架重组，我们研究了它们可能的相互作用。我们在此表明，相当一部分Rac1与Rab11阳性循环内体相关联。此外，Rab11效应器FIP3控制Rac1在细胞内的定位以及Rac1靶向免疫突触。FIP3以Rac1依赖的方式调节关键的形态学事件，如T细胞铺展和突触对称性。最后，Rab11-/FIP3介导的调节对于导致细胞因子产生的T细胞活化是必需的。因此，Rac1内体运输是调节T细胞活化的关键。
