2026-06-14T03:40:24Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/51772024-09-27T08:00:45Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Castro-Castro, Antonio author Muriel, Olivia author del Pozo, Miguel Angel author Bustelo, Xose R. author 2016 The Rac1 GTPase plays key roles in cytoskeletal organization, cell motility and a variety of physiological and disease-linked responses. Wild type Rac1 signaling entails dissociation of the GTPase from cytosolic Rac1-Rho GDP dissociation inhibitor (GDI) complexes, translocation to membranes, activation by exchange factors, effector binding, and activation of downstream signaling cascades. Out of those steps, membrane translocation is the less understood. Using transfections of a expression cDNA library in cells expressing a Rac1 bioreporter, we previously identified a cytoskeletal feedback loop nucleated by the F-actin binding protein coronin 1A (Coro1A) that promotes Rac1 translocation to the plasma membrane by facilitating the Pak-dependent dissociation of Rac1-Rho GDI complexes. This screening identified other potential regulators of this process, including WDR26, basigin, and TMEM8A. Here, we show that WDR26 promotes Rac1 translocation following a Coro1A-like and Coro1A-dependent mechanism. By contrast, basigin and TMEM8A stabilize Rac1 at the plasma membrane by inhibiting the internalization of caveolin-rich membrane subdomains. This latter pathway is F-actin-dependent but Coro1A-, Pak- and Rho GDI-independent. PLoS One. 2016; 11(11):e0166715 10.1371/journal.pone.0166715 1932-6203 PLoS One 27835684 http://hdl.handle.net/20.500.12105/5177 INTEGRIN-ASSOCIATED PROTEIN SMALL GTPASE RAC G-BETA-GAMMA CELL-MIGRATION PLASMA-MEMBRANE CORONIN 1A SIGNAL-TRANSDUCTION LIPID RAFTS ACTIVATION DISSOCIATION Characterization of Novel Molecular Mechanisms Favoring Rac1 Membrane Translocation