TY - JOUR
T1 - 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
AU - Martins, Aline Fagundes
AU - Xavier Neto, José
AU - Azambuja, Ana
AU - Sereno, Maria Lorena
AU - Figueira, Antonio
AU - Campos-Junior, Paulo Henrique
AU - Rosário, Millor Fernandes
AU - Toledo, Cristiane Bittencourt Barroso
AU - Silva, Gerluza Aparecida Borges
AU - Kitten, Gregory Thomas
AU - Coutinho, Luiz Lehmann
AU - Dietrich, Susanne
AU - Jorge, Erika Cristina
N1 - © 2015 S. Karger AG, Basel.
PY - 2015/9
Y1 - 2015/9
N2 - 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.
AB - 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.
U2 - 10.1159/000433491
DO - 10.1159/000433491
M3 - Article
C2 - 26397945
SN - 1422-6405
VL - 200
SP - 326
EP - 338
JO - Cells, tissues, organs
JF - Cells, tissues, organs
IS - 5
ER -