title: Liprin-α controls stress fiber formation by binding to mDia and regulating its membrane localization.
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 N-terminal 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 mDia-binding 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.
authors.affiliation: Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Sakamoto
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Ishizaki
authors.forename: Katsuya
authors.initials: K
authors.lastname: Okawa
authors.forename: Sadanori
authors.initials: S
authors.lastname: Watanabe
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Arakawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Watanabe
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D000080865:Formins; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism*; D022502:Stress Fibers / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C108962:DIAPH1 protein, human; D000080865:Formins; C094398:PPFIA1 protein, human; C477798:Ppfia1 protein, mouse; D011506:Proteins