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Review
. 2018 Jul 4;9(4):310-315.
doi: 10.1080/21541248.2016.1224288. Epub 2016 Sep 2.

The functional interplay of Rab11, FIP3 and Rho proteins on the endosomal recycling pathway controls cell shape and symmetry

Jérôme Bouchet  1   2   3 , Mary W McCaffrey  4 , Andrea Graziani  5 , Andrés Alcover  1   2
Affiliations
Review

The functional interplay of Rab11, FIP3 and Rho proteins on the endosomal recycling pathway controls cell shape and symmetry

Jérôme Bouchet et al. Small GTPases. .

Abstract

Several families of small GTPases regulate a variety of fundamental cellular processes, encompassing growth factor signal transduction, vesicular trafficking and control of the cytoskeleton. Frequently, their action is hierarchical and complementary, but much of the detail of their functional interactions remains to be clarified. It is well established that Rab family members regulate a variety of intracellular vesicle trafficking pathways. Moreover, Rho family GTPases are pivotal for the control of the actin and microtubule cytoskeleton. However, the interplay between these 2 types of GTPases has been rarely reported. We discuss here our recent findings showing that Rab11, a key regulator of endosomal recycling, and Rac1, a central actin cytoskeleton regulator involved in lamellipodium formation and cell migration, interplay on endosomes through the Rab11 effector FIP3. In the context of the rapidly reactive T lymphocytes, Rab11-Rac1 endosomal functional interplay is important to control cell shape changes and cell symmetry during lymphocyte spreading and immunological synapse formation and ultimately modulate T cell activation.

Keywords: FIP3; immunological synapse; Rab11; Rac; T cell activation; cell shape; cell symmetry; recycling endosomes.

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Figures

Figure 1.
Figure 1.
Structure of Rab11-FIPs. Classification and schematic representation of FIPs predicted domain architecture: C2-domain (C2); PEST domain (PEST), coiled-coil domain (CC), Rab-binding domain (RBD), Prolin-Rich domain, EF-hand domain (EF); Arf-binding domain (ABD). According to Horgan and McCaffrey.
Figure 2.
Figure 2.
Model for Rab11-Rac1 interplay. After internalization, Rac1 is targeted to early/sorting endosomes, where its traffic is taken in charge by Rab11. Via its interaction with FIP3 and with the help of Rab11 and dynein complex, Rac1 carrying vesicles migrate to the endosomal recycling compartment. Rac1 recycling back to the plasma membrane may involve Rab11 associated to FIP3 or to type I FIPs both interacting with kinesin that drives outward vesicle movement. Finally, interaction of FIP3 with the exocyst complex would facilitate the targeting and release of Rac1 carrying vesicles to the plasma membrane.
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Grants and funding

The authors were supported by grants from the Agence National de Recherche sur le SIDA et les Hepatitis Virales (ANRS), Roux-Institut Pasteur and Sidaction to JB; Agence Nationale de Recherche (ANR, No 11 BSV3 025 01), ANRS (AO 2013-02 CSS1 No 1339/14673), Institut Pasteur, CNRS and INSERM to AA; Science Foundation Ireland Principal Investigator Award (09/IN.1/B2629) to MWM; Fondazione Telethon GGP13254 and AIRC (Italian Association for Cancer Research) IG13524 to AG.

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