title: Repulsive Guidance Molecules a, b and c Are Skeletal Muscle Proteins, and Repulsive Guidance Molecule a Promotes Cellular Hypertrophy and Is Necessary for Myotube Fusion.
abstract: Repulsive guidance molecules (RGMs) compose a family of glycosylphosphatidylinositol (GPI)-anchored axon guidance molecules and perform several functions during neural development. New evidence has suggested possible new roles for these axon guidance molecules during skeletal muscle development, which has not been investigated thus far. In the present study, we show that RGMa, RGMb and RGMc are all induced during skeletal muscle differentiation in vitro. Immunolocalization performed on adult skeletal muscle cells revealed that RGMa, RGMb and RGMc are sarcolemmal proteins. Additionally, RGMa was found to be a sarcoplasmic protein with a surprisingly striated pattern. RGMa colocalization with known sarcoplasmic proteins suggested that this axon guidance molecule is a skeletal muscle sarcoplasmic protein. Western blot analysis revealed two RGMa fragments of 60 and 33 kDa, respectively, in adult skeletal muscle samples. RGMa phenotypes in skeletal muscle cells (C2C12 and primary myoblasts) were also investigated. RGMa overexpression produced hypertrophic cells, whereas RGMa knockdown resulted in the opposite phenotype. RGMa knockdown also blocked myotube formation in both skeletal muscle cell types. Our results are the first to show an axon guidance molecule as a skeletal muscle sarcoplasmic protein and to include RGMa in a system that regulates skeletal muscle cell size and differentiation.
authors.affiliation: Departamento de Morfologia, Instituto de Cix00EA;ncias Biolx00F3;gicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: Aline Fagundes
authors.initials: AF
authors.lastname: Martins
authors.forename: José
authors.initials: J
authors.lastname: Xavier Neto
authors.forename: Ana
authors.initials: A
authors.lastname: Azambuja
authors.forename: Maria Lorena
authors.initials: ML
authors.lastname: Sereno
authors.forename: Antonio
authors.initials: A
authors.lastname: Figueira
authors.forename: Paulo Henrique
authors.initials: PH
authors.lastname: Campos-Junior
authors.forename: Millor Fernandes
authors.initials: MF
authors.lastname: Rosário
authors.forename: Cristiane Bittencourt Barroso
authors.initials: CB
authors.lastname: Toledo
authors.forename: Gerluza Aparecida Borges
authors.initials: GA
authors.lastname: Silva
authors.forename: Gregory Thomas
authors.initials: GT
authors.lastname: Kitten
authors.forename: Luiz Lehmann
authors.initials: LL
authors.lastname: Coutinho
authors.forename: Susanne
authors.initials: S
authors.lastname: Dietrich
authors.forename: Erika Cristina
authors.initials: EC
authors.lastname: Jorge
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D049108:Cell Enlargement; D006984:Hypertrophy / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D024510:Muscle Development / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins