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Citation
Neisch, A.L., Formstecher, E., Fehon, R.G. (2013). Conundrum, an ARHGAP18 orthologue, regulates RhoA and proliferation through interactions with Moesin.  Mol. Biol. Cell 24(9): 1420--1433.
FlyBase ID
FBrf0223340
Publication Type
Research paper
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.

PubMed ID
PubMed Central ID
PMC3639053 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Mol. Biol. Cell
    Title
    Molecular Biology of the Cell
    Publication Year
    1992-
    ISBN/ISSN
    1059-1524
    Data From Reference
    Aberrations (3)
    Alleles (27)
    Gene Groups (2)
    Genes (20)
    Physical Interactions (7)
    Cell Lines (1)
    Natural transposons (1)
    Insertions (4)
    Experimental Tools (4)
    Transgenic Constructs (23)