From T-tubule to sarcolemma: damage-induced dysferlin translocation in early myogenesis.
The dysferlin gene is mutated in limb-girdle muscular dystrophy type 2B, Miyoshi myopathy, and distal anterior compartment myopathy. In mature skeletal muscle, dysferlin is located predominantly at the sarcolemma, where it plays a role in membrane fusion and repair. To investigate the role of dysferlin during early muscle differentiation, its localization was studied at high resolution in a muscle cell line. This demonstrated that dysferlin is not expressed at the plasmalemma of myotubes but mostly localizes to the T-tubule network. However, dysferlin translocated to the site of injury and toward the plasma membrane in a Ca2+-dependent fashion in response to a newly designed in vitro wounding assay. This reaction was specific to the full-length protein, as heterologously expressed deletion mutants of distinct C2 domains of dysferlin did not show this response. These results shed light on the dynamics of muscle membrane repair and are highly indicative of a specific role of dysferlin in this process in early myogenesis.
Klinge
Lars
L
Institute of Human Genetics, University of Newcastle upon Tyne, International Centre for Life, Central Pkwy, NE1 3BZ Newcastle upon Tyne, England, UK.
Laval
Steve
S
Keers
Sharon
S
Haldane
Faye
F
Straub
Volker
V
Barresi
Rita
R
Bushby
Kate
K
D002454:Cell Differentiation; D002460:Cell Line; D000073939:Dysferlin; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D009135:Muscular Diseases / Q000473:pathology; D021381:Protein Transport; D012508:Sarcolemma / Q000473:pathology; D014947:Wounds and Injuries
C114839:DYSF protein, human; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins