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The atypical Rho GTPase RhoU interacts with intersectin-2 to regulate endosomal recycling pathways
Author(s) -
Olga Gubar,
Pauline Croisé,
S. V. Kropyvko,
T. A. Gryaznova,
Petra Toth,
Anne Blangy,
Nicolas Vitale,
A. V. Rynditch,
Stéphane Gasman,
Stéphane Ory
Publication year - 2020
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.234104
Subject(s) - endosome , microbiology and biotechnology , biology , gtpase , vesicle , cdc42 , endomembrane system , endocytosis , rab , small gtpase , vesicular transport protein , signal transducing adaptor protein , endocytic cycle , transport protein , cell , signal transduction , membrane , golgi apparatus , biochemistry , endoplasmic reticulum , intracellular
Rho GTPases play a key role in various membrane trafficking processes. RhoU is an atypical small Rho GTPase related to Rac/Cdc42 which possesses unique N- and C-terminal domains that regulate its function and its subcellular localization. RhoU localized at the plasma membrane, on endosomes and in cell adhesion structures where it governs cell signalling, differentiation and migration. However, despite its endomembrane localization, RhoU function in vesicular trafficking has been unexplored. Here, we identified intersectins (ITSNs) as new binding partners for RhoU and showed that the second PxxP motif at the N-terminus of RhoU mediated interactions with SH3 domains of ITSNs. To evaluate the function of RhoU and ITSNs in vesicular trafficking, we used fluorescent transferrin as a cargo for uptake experiments. We showed that silencing of either RhoU or ITSN2, but not ITSN1 increased transferrin accumulation in early endosomes resulting from defect in fast vesicle recycling. Concomitantly, RhoU and ITSN2 colocalized to a subset of Rab4-positive vesicles suggesting that RhoU-ITSN2 interaction may occur on fast recycling endosomes to regulate the fate of vesicular cargos.

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