RRC ID 28080
Author Neisch AL, Formstecher E, Fehon RG.
Title Conundrum, an ARHGAP18 orthologue, regulates RhoA and proliferation through interactions with Moesin.
Journal Mol. Biol. Cell
Abstract RhoA, a small GTPase, regulates epithelial integrity and morphogenesis by controlling filamentous actin assembly and actomyosin contractility. Another important cytoskeletal regulator, Moesin (Moe), an ezrin, radixin, and moesin (ERM) protein, has the ability to bind to and organize cortical F-actin, as well as the ability to regulate RhoA activity. ERM proteins have previously been shown to interact with both RhoGEF (guanine nucleotide exchange factors) and RhoGAP (GTPase activating proteins), proteins that control the activation state of RhoA, but the functions of these interactions remain unclear. We demonstrate that Moe interacts with an unusual RhoGAP, Conundrum (Conu), and recruits it to the cell cortex to negatively regulate RhoA activity. In addition, we show that cortically localized Conu can promote cell proliferation and that this function requires RhoGAP activity. Surprisingly, Conu's ability to promote growth also appears dependent on increased Rac activity. Our results reveal a molecular mechanism by which ERM proteins control RhoA activity and suggest a novel linkage between the small GTPases RhoA and Rac in growth control.
Volume 24(9)
Pages 1420-33
Published 2013-5
DOI 10.1091/mbc.E12-11-0800
PII mbc.E12-11-0800
PMID 23468526
PMC PMC3639053
MeSH Animals Cell Line Cell Membrane / metabolism Cell Proliferation* Cell Shape Cell Survival Compound Eye, Arthropod / metabolism Drosophila Proteins / metabolism* Drosophila Proteins / physiology* Drosophila melanogaster / cytology Drosophila melanogaster / metabolism* Epithelial Cells / physiology Epithelium / metabolism Female GTPase-Activating Proteins / genetics GTPase-Activating Proteins / physiology* Imaginal Discs / metabolism Male Membrane Proteins / metabolism* Protein Binding Protein Interaction Domains and Motifs Protein Interaction Mapping Protein Stability Protein Transport rho GTP-Binding Proteins / metabolism*
IF 3.905
Times Cited 9