Liprin-α controls stress fiber formation by binding to mDia and regulating its membrane localization

Satoko Sakamoto, Toshimasa Ishizaki, Katsuya Okawa, Sadanori Watanabe, Takatoshi Arakawa, Naoki Watanabe, Shuh Narumiya

    Research output: Contribution to journalArticle

    24 Citations (Scopus)

    Abstract

    Regulation of the actin cytoskeleton is crucial for cell morphology and migration. mDia is an actin nucleator that produces unbranched actin filaments downstream of Rho. However, the mechanisms by which mDia activity is regulated in the cell remain unknown. We pulled down Liprin-α as an mDia-binding protein. The binding is mediated through the central region of Liprin-α and through the Nterminal Dia-inhibitory domain (DID) and dimerization domain (DD) of mDia. Liprin-α competes with Dia autoregulatory domain (DAD) for binding to DID, and binds preferably to the open form of mDia. Overexpression of a Liprin-α fragment containing the mDiabinding region decreases localization of mDia to the plasma membrane and attenuates the Rho-mDia-mediated formation of stress fibers in cultured cells. Conversely, depletion of Liprin-α by RNA interference (RNAi) increases the amount of mDia in the membrane fraction and enhances formation of actin stress fibers. Thus, Liprin-α negatively regulates the activity of mDia in the cell by displacing it from the plasma membrane through binding to the DID-DD region.

    Original languageEnglish
    Pages (from-to)108-120
    Number of pages13
    JournalJournal of cell science
    Volume125
    Issue number1
    DOIs
    Publication statusPublished - 2012 Jan 1

    Keywords

    • Actin cytoskeleton
    • Liprin-α
    • Mdia
    • Rho

    ASJC Scopus subject areas

    • Cell Biology

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    Sakamoto, S., Ishizaki, T., Okawa, K., Watanabe, S., Arakawa, T., Watanabe, N., & Narumiya, S. (2012). Liprin-α controls stress fiber formation by binding to mDia and regulating its membrane localization. Journal of cell science, 125(1), 108-120. https://doi.org/10.1242/jcs.087411