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ARHGAP22 Localizes at Endosomes and Regulates Actin Cytoskeleton
Rho small GTPases control cell morphology and motility through the rearrangement of actin cytoskeleton. We have previously shown that FilGAP, a Rac-specific GAP, binds to the actin-cross-linking protein Filamin A (FLNa) and suppresses Rac-dependent lamellae formation and cell spreading. ARHGAP22 is...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4059726/ https://www.ncbi.nlm.nih.gov/pubmed/24933155 http://dx.doi.org/10.1371/journal.pone.0100271 |
Sumario: | Rho small GTPases control cell morphology and motility through the rearrangement of actin cytoskeleton. We have previously shown that FilGAP, a Rac-specific GAP, binds to the actin-cross-linking protein Filamin A (FLNa) and suppresses Rac-dependent lamellae formation and cell spreading. ARHGAP22 is a member of FilGAP family, and implicated in the regulation of tumor cell motility. However, little is known concerning the cellular localization and mechanism of regulation at the molecular level. Whereas FilGAP binds to FLNa and localizes to lamellae, we found that ARHGAP22 did not bind to FLNa. Forced expression of ARHGAP22 induced enlarged vesicular structures containing the endocytic markers EEA1, Rab5, and Rab11. Moreover, endogenous ARHGAP22 is co-localized with EEA1- and Rab11-positive endosomes but not with trans-Golgi marker TNG46. When constitutively activated Rac Q61L mutant was expressed, ARHGAP22 is co-localized with Rac Q61L at membrane ruffles, suggesting that ARHGAP22 is translocated from endosomes to membrane ruffles to inactivate Rac. Forced expression of ARHGAP22 suppressed lamellae formation and cell spreading. Conversely, knockdown of endogenous ARHGAP22 stimulated cell spreading. Thus, our findings suggest that ARHGAP22 controls cell morphology by inactivating Rac but its localization is not mediated by its interaction with FLNa. |
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