title: The N-BAR domain protein, Bin3, regulates Rac1- and Cdc42-dependent processes in myogenesis.
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.
authors.affiliation: Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University School of Medicine, Atlanta, GA 30322, USA; Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Simionescu-Bankston
authors.forename: Giovanna
authors.initials: G
authors.lastname: Leoni
authors.forename: Yanru
authors.initials: Y
authors.lastname: Wang
authors.forename: Peter P
authors.initials: PP
authors.lastname: Pham
authors.forename: Arivudainambi
authors.initials: A
authors.lastname: Ramalingam
authors.forename: James B
authors.initials: JB
authors.lastname: DuHadaway
authors.forename: Victor
authors.initials: V
authors.lastname: Faundez
authors.forename: Asma
authors.initials: A
authors.lastname: Nusrat
authors.forename: George C
authors.initials: GC
authors.lastname: Prendergast
authors.forename: Grace K
authors.initials: GK
authors.lastname: Pavlath
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D004705:Endocytosis; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000737:chemistry* / Q000172:deficiency / Q000378:metabolism*; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D009479:Neuropeptides / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011554:Pseudopodia / Q000378:metabolism; D012038:Regeneration; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; C581598:Cdc42 protein, mouse; D008840:Microfilament Proteins; D009479:Neuropeptides; C484602:Rac1 protein, mouse; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein
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