The atypical Rho GTPase RhoU interacts with intersectin-2 to regulate endosomal recycling pathways.

Fiche publication


Date publication

juillet 2020

Journal

Journal of cell science

Auteurs

Membres identifiés du Cancéropôle Est :
Dr GASMAN Stéphane, Dr VITALE Nicolas, Dr TOTH Petra, Dr ORY Stéphane


Tous les auteurs :
Gubar O, Croisé P, Kropyvko S, Gryaznova T, Toth P, Blangy A, Vitale N, Rynditch A, Gasman S, Ory S

Résumé

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.

Mots clés

Atypical Rho GTPases, Intersectins, Proline rich domains, SH3 domains, Vesicle recycling

Référence

J. Cell. Sci.. 2020 Jul 31;: