Spatiotemporal Control of Actin Assembly at the Leading Edge by IQGAP

Gregory Hoeprich, Maria Angeles Juanes, Bruce L. Goode

    Research output: Contribution to journalConference articlepeer-review

    Abstract

    Cell migration requires precise spatial and temporal control of the actin cytoskeleton, which is regulated
    by multiple actin binding proteins. Recent work has revealed adenomatous polyposis coli (APC) is a
    potent actin nucleator in vitro and works collaboratively with formins to assemble actin filaments by a
    ‘Rocket Launcher’ mechanism (Breitsprecher et al., 2012). Further, it was found that APC‐mediated actin
    nucleation occurs at focal adhesions, where it is critical for microtubule‐induce focal adhesion turnover
    and directed cell migration (Juanes et al, 2017). These and other observations suggest that APC, formins,
    and other key binding partners such as CLIP‐170 may work in concert to control actin assembly
    underlying cell migration. Here, we have investigated how IQGAP mechanistically influences actin
    assembly, alone and together with APC, formins, and CLIP‐170. IQGAP is a multi‐domain scaffolding
    protein that bundles F‐actin, caps barbed ends, and binds directly to APC, the formin Dia1, and CLIP‐170.
    Using TIRF microscopy, we have begun defining the effects of full‐length IQGAP on actin assembly
    dynamics, alone and in the presence of these other factors. Our preliminary in vitro observations
    suggest that IQGAP attenuates actin assembly by APC and Dia1, and consistent with these effects, RNAi
    silencing of IQGAP in HeLa cells led to excessive actin accumulation at the leading edge. Thus, IQGAP
    may restrain unregulated actin assembly at the leading edge until specific signals are received, and in
    this manner spatially and temporally control cell migration.
    Original languageEnglish
    Article numberP1952
    Pages (from-to)605
    JournalMolecular Biology of the Cell
    Volume28
    Publication statusPublished - 31 Jan 2017
    Event2017 Annual Joint Meeting of the American Society for Cell Biology and the European Molecular Biology Organization - Philadelphia, United States
    Duration: 2 Dec 20176 Dec 2017

    Bibliographical note

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739290/

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