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; BAR domain; Bin; Bin-Amphiphysin-Rvs; Bridging integrator; CSA; Cdc42; Cross-sectional area; DM; Differentiation media; Embryonic myosin heavy chain; F-actin; Filamentous actin; GAP; GEF; GM; GRAF1; GTPase regulator associated with focal adhesion kinase-1; GTPase-activating protein; Growth media; Guanine nucleotide exchange factor; KO; Knockout; Muscle regeneration; Myogenesis; PAK; PBDp21-binding; RV; Rac1; Retrovirus; WT; Wild-type; domain; eMyHC; p21-activated protein kinase.
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