Rac1‐Rab11‐FIP3 regulatory hub coordinates vesicle traffic with actin remodeling and T‐cell activation |
| |
| Authors: | Jérôme Bouchet Iratxe del Río‐Iñiguez Rémi Lasserre Sonia Agüera‐Gonzalez Céline Cuche Anne Danckaert Mary W McCaffrey Vincenzo Di Bartolo Andrés Alcover |
| |
| Institution: | 1. Lymphocyte Cell Biology Unit, Department of Immunology, Institut Pasteur, Paris, France;2. CNRS URA 1961, Paris, France;3. INSERM U1221, Paris, France;4. Institut Pasteur Citech‐Imagopole, Paris, France;5. Molecular Cell Biology Laboratory, Biosciences Institute, School of Biochemistry and Cell Biology, University College Cork, Cork, Ireland |
| |
| Abstract: | 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. |
| |
| Keywords: | actin cytoskeleton immunological synapse intracellular traffic Rab11‐FIP3 Rac1 recycling endosomes |
|
|
