MG53 regulates membrane budding and exocytosis in muscle cells.
Membrane recycling and remodeling contribute to multiple cellular functions, including cell fusion events during myogenesis. We have identified a tripartite motif (TRIM72) family member protein named MG53 and defined its role in mediating the dynamic process of membrane fusion and exocytosis in striated muscle. MG53 is a muscle-specific protein that contains a TRIM motif at the amino terminus and a SPRY motif at the carboxyl terminus. Live cell imaging of green fluorescent protein-MG53 fusion construct in cultured myoblasts showed that although MG53 contains no transmembrane segment it is tightly associated with intracellular vesicles and sarcolemmal membrane. RNA interference-mediated knockdown of MG53 expression impeded myoblast differentiation, whereas overexpression of MG53 enhanced vesicle trafficking to and budding from sarcolemmal membrane. Co-expression studies indicated that MG53 activity is regulated by a functional interaction with caveolin-3. Our data reveal a new function for TRIM family proteins in regulating membrane trafficking and fusion in striated muscles.
Cai
Chuanxi
C
Departments of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854.
Masumiya
Haruko
H
Department of Medical Chemistry, Tohoku University Graduate School of Medicine, Miyagi 980-8575, Japan.
Weisleder
Noah
N
Departments of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854.
Pan
Zui
Z
Departments of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854.
Nishi
Miyuki
M
Department of Medical Chemistry, Tohoku University Graduate School of Medicine, Miyagi 980-8575, Japan; Department of Biological Chemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto 606-8501, Japan.
Komazaki
Shinji
S
Department of Anatomy, Saitama Medical University, Saitama 350-0495, Japan.
Takeshima
Hiroshi
H
Department of Medical Chemistry, Tohoku University Graduate School of Medicine, Miyagi 980-8575, Japan; Department of Biological Chemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Kyoto 606-8501, Japan. Electronic address: takeshim@pharm.kyoto-u.ac.jp.
Ma
Jianjie
J
Departments of Physiology and Biophysics, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854; Department of Medicine, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854. Electronic address: maj2@umdnj.edu.
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000302:isolation & purification; D006224:Cricetinae; D017931:DNA Primers; D005089:Exocytosis / Q000502:physiology*; D008565:Membrane Proteins; D051379:Mice; D008854:Microscopy, Electron; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport; D034622:RNA Interference
D002352:Carrier Proteins; D017931:DNA Primers; C538824:MG53 protein, mouse; D008565:Membrane Proteins; D002784:Cholesterol