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

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 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.
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https://hal-pasteur.archives-ouvertes.fr/pasteur-01370720
Contributor : Vincenzo Di Bartolo <>
Submitted on : Friday, September 23, 2016 - 11:37:00 AM
Last modification on : Friday, October 23, 2020 - 4:35:01 PM

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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, EMBO Press, 2016, ⟨10.15252/embj.201593274⟩. ⟨pasteur-01370720⟩

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