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Avidity‐driven polarity establishment via multivalent lipid– GTP ase module interactions
Author(s) -
Meca Julien,
MassoniLaporte Aurélie,
Martinez Denis,
Sartorel Elodie,
Loquet Antoine,
Habenstein Birgit,
McCusker Derek
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201899652
Subject(s) - guanine nucleotide exchange factor , gtpase , cdc42 , biology , cell polarity , scaffold protein , microbiology and biotechnology , avidity , biophysics , gtpase activating protein , polarity (international relations) , plasma protein binding , biochemistry , signal transduction , cell , g protein , genetics , antibody
Abstract While Rho GTP ases are indispensible regulators of cellular polarity, the mechanisms underlying their anisotropic activation at membranes have been elusive. Using the budding yeast Cdc42 GTP ase 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 GTP ase activation.