Journal
EMBO JOURNAL
Volume 35, Issue 11, Pages 1160-1174Publisher
WILEY
DOI: 10.15252/embj.201593274
Keywords
actin cytoskeleton; immunological synapse; intracellular traffic; Rab11-FIP3; Rac1; recycling endosomes
Categories
Funding
- Agence Nationale de Recherche (ANR) [11 BSV3 025 01]
- Agence National de Recherche sur le SIDA et les Hepatitis Virales (ANRS) [AO 2013-02 CSS1, 13391/14673]
- Institut Pasteur
- CNRS
- People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/ under the REA grant [317057]
- ANRS Postdoctoral Fellowship
- Roux-Institut Pasteur Postdoctoral Fellowship
- European Union Marie Curie Actions Initial Training Network HOMIN Predoctoral Fellowship
- ANR
- Fondation ARC pour la Recherche sur le Cancer
- [ANR-10-INSB-04-01]
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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.
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