2024-03-28T09:30:30Zhttp://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
Repisalud
author
Castro-Castro, Antonio
author
Muriel, Olivia
author
del Pozo, Miguel Angel
author
Bustelo, Xose R.
funder
Ministerio de Economía y Competitividad (España)
funder
Worldwide Cancer Research
funder
Fundación Ramón Areces
funder
Asociación Española Contra el Cáncer
funder
Junta de Castilla y León (España)
2017-10-20T10:33:51Z
2017-10-20T10:33:51Z
2016
PLoS One. 2016; 11(11):e0166715
1932-6203
http://hdl.handle.net/20.500.12105/5177
27835684
10.1371/journal.pone.0166715
PLoS One
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.
eng
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
journal article
URL
https://repisalud.isciii.es/bitstream/20.500.12105/5177/1/CharacterizationOfNovelMolecular_2016.pdf
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MD5
6917667d3d8f6d29079a2e124b38314b
3529700
application/pdf
CharacterizationOfNovelMolecular_2016.pdf
URL
https://repisalud.isciii.es/bitstream/20.500.12105/5177/8/CharacterizationOfNovelMolecular_2016.pdf.txt
File
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a11b45a140b8732781f278b041e38765
76066
text/plain
CharacterizationOfNovelMolecular_2016.pdf.txt