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

• Type of Material: Article
• Authors: Adriana Simionescu-Bankston, Emory University; Giovanna Leoni, Emory University; Yanru Wang, Loyola University; Peter P. Pham, Emory University; Arivudainambi Ramalingam, Tulane University; James B. DuHadaway, Lankenau Institute for Medical Research; Victor Faundez, Emory University; Asma Nusrat, Emory University; George C. Prendergast, Lankenau Institute for Medical Research; Grace K Pavlath, Emory University
• Language: English
• Date: 2013-10-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ydbio.2013.07.004
• Title of Journal or Parent Work: Developmental Biology
• ISSN: 0012-1606
• Volume: 382
• Issue: 1
• Start Page: 160
• End Page: 171
• Grant/Funding Information: This work was supported by grants from the National Institutes of Health (AR-04731408 to G.K.P.; DK59888 to A.N.; GM077569 and NS42599 to V.F.); and from the Emory University Research Committee to V.F.
• Keywords: Cdc42; BAR domain; Rac1; Myogenesis; Muscle regeneration; ADHESION; GTPASE-ACTIVATING PROTEIN; CELL DIFFERENTIATION; F-actin; MIGRATION; SKELETAL-MUSCLE REGENERATION; FISSION; Science & Technology; MYOBLAST FUSION; Developmental Biology; Life Sciences & Biomedicine; ATOMIC-FORCE MICROSCOPY; MACROPHAGES; PATHWAY
• Research Categories: Biology, Cell; Health Sciences, Pathology; Chemistry, Biochemistry

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.