Rac1-Rab11-FIP3 regulatory hub coordinates vesicle traffic with actin remodeling and T-cell activation

Jérôme Bouchet (1, 2) , Iratxe del Río-Iñiguez (2, 1) , Rémi Lasserre (2) , Sonia Agüera-Gonzalez (2) , Céline Cuche (2, 1) , Anne Danckaert (3) , Mary W Mccaffrey (4) , Vincenzo Di Bartolo (2, 1) , Andrés Alcover (2, 1)

1 BIOCELLY - Biologie Cellulaire des Lymphocytes
2 Biologie Cellulaire des Lymphocytes - Lymphocyte Cell Biology
3 CITECH - Imagopole
4 UCC - University College Cork

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 intracellu-lar vesicle traffic. However, how these events are coordinated is ill defined. Since Rab and Rho families of GTPases control intracellu-lar 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 intra-cellular 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.

Mots clés: recycling endosomes Subject Categories Cell Adhesion; Rac1; intracellular traffic; Rab11-FIP3; actin cytoskeleton; immunological synapse; Polarity & Cytoskeleton; Immunology; Membrane & Intracellular Transport

Domaines: Immunité adaptative; Organisation et fonctions cellulaires [q-bio.SC]

Jérôme Bouchet, Iratxe del Río-Iñiguez, Rémi Lasserre, Sonia Agüera-Gonzalez, Céline Cuche, et al.. Rac1-Rab11-FIP3 regulatory hub coordinates vesicle traffic with actin remodeling and T-cell activation. EMBO Journal, 2016, ⟨10.15252/embj.201593274⟩. ⟨pasteur-01370720⟩