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The N-BAR domain protein,Bin3, regulates Rac1- and Cdc42-dependent processes in myogenesis
Authors:Adriana Simionescu-Bankston  Giovanna Leoni  Yanru Wang  Peter P. Pham  Arivudainambi Ramalingam  James B. DuHadaway  Victor Faundez  Asma Nusrat  George C. Prendergast  Grace K. Pavlath
Affiliation:1. Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University School of Medicine, Atlanta, GA 30322, USA;2. Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA;3. Department of Pathology and Laboratory Medicine, Epithelial Pathobiology and Mucosal Inflammation Research Unit, Emory University School of Medicine, Atlanta, GA 30322, USA;4. Department of Cell & Molecular Physiology, Loyola University Chicago, Maywood, IL 60153, USA;5. Hayward Genetics Center, Tulane University School of Medicine, New Orleans, LA 70112, USA;6. Lankenau Institute for Medical Research, Wynnewood, PA 19096, USA;g Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA
Abstract:Actin dynamics are necessary at multiple steps in the formation of multinucleated muscle cells. BAR domain proteins can regulate actin dynamics in several cell types, but have been little studied in skeletal muscle. Here, we identify novel functions for the N-BAR domain protein, Bridging integrator 3 (Bin3), during myogenesis in mice. Bin3 plays an important role in regulating myofiber size in vitro and in vivo. During early myogenesis, Bin3 promotes migration of differentiated muscle cells, where it colocalizes with F-actin in lamellipodia. In addition, Bin3 forms a complex with Rac1 and Cdc42, Rho GTPases involved in actin polymerization, which are known to be essential for myotube formation. Importantly, a Bin3-dependent pathway is a major regulator of Rac1 and Cdc42 activity in differentiated muscle cells. Overall, these data classify N-BAR domain proteins as novel regulators of actin-dependent processes in myogenesis, and further implicate BAR domain proteins in muscle growth and repair.
Keywords:BAR, Bin-Amphiphysin-Rvs   Bin, Bridging integrator   CSA, Cross-sectional area   DM, Differentiation media   eMyHC, Embryonic myosin heavy chain   F-actin, Filamentous actin   GAP, GTPase-activating protein   GEF, Guanine nucleotide exchange factor   GM, Growth media   GRAF1, GTPase regulator associated with focal adhesion kinase-1   KO, Knockout   PAK, p21-activated protein kinase   PBDp21-binding, domain   RV, Retrovirus   WT, Wild-type
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