2024-03-28T09:33:06Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/51772022-09-29T11:42:43Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
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
1932-6203
http://hdl.handle.net/20.500.12105/5177
27835684
10.1371/journal.pone.0166715
PLoS One
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