While Rho GTPases are indispensible regulators of cellular polarity, the mechanisms underlying their anisotropic activation at membranes have been elusive. Using the budding yeast Cdc42 GTPase module, which includes a guanine nucleotide exchange factor (GEF) Cdc24 and the scaffold Bem1, we find that avidity generated via multivalent anionic lipid interactions is a critical mechanistic constituent of polarity establishment. We identify basic cluster (BC) motifs in Bem1 that drive the interaction of the scaffold-GEF complex with anionic lipids at the cell pole. This interaction appears to influence lipid acyl chain ordering, thus regulating membrane rigidity and feedback between Cdc42 and the membrane environment. Sequential mutation of the Bem1 BC motifs, PX domain, and the PH domain of Cdc24 lead to a progressive loss of cellular polarity stemming from defective Cdc42 nanoclustering on the plasma membrane and perturbed signaling. Our work demonstrates the importance of avidity via multivalent anionic lipid interactions in the spatial control of GTPase activation.< Réduire

Mots clés en anglais

cell polarity

lipids

nanoclustering

Rho GTPase

super‐resolution imaging

Project ANR

Régulation et dynamique d'un module de signaliation de la famille Rhoulation and dynamics of a GTPase signaling module - ANR-13-BSV2-0015
Nanostructures biologiques et synthétiques étudiées par Résonance Magnétique Nucléaire du Solide - ANR-14-CE09-0020

Unités de recherche

CBMN : Chimie & de Biologie des Membranes & des Nano-objets - UMR 5248

Voir/Ouvrir

Métadonnées

Partager cette publication !

Licence d’utilisation du document

Avidity-driven polarity establishment via multivalent lipid-GTPase module interactions

Langue

Ce document a été publié dans

Résumé en anglais

Mots clés en anglais

URI

DOI

Lien vers les données de la recherche

Project ANR

Unités de recherche