The N-BAR domain protein,Bin3, regulates Rac1- and Cdc42-dependent processes in myogenesis |
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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 |
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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 |
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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. |
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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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