Dysferlin associates with the developing T-tubule system in rodent and human skeletal muscle.
Mutations in the dysferlin gene cause limb-girdle muscular dystrophy type 2B, Miyoshi myopathy, and distal anterior compartment myopathy. Dysferlin mainly localizes to the sarcolemma in mature skeletal muscle where it is implicated in membrane fusion and repair. In different forms of muscular dystrophy, a predominantly cytoplasmic localization of dysferlin can be observed in regenerating myofibers, but the subcellular compartment responsible for this labeling pattern is not yet known. We have previously demonstrated an association of dysferlin with the developing T-tubule system in vitro. To investigate the role of dysferlin in adult skeletal muscle regeneration, we studied dysferlin localization at high resolution in a rat model of regeneration and found that the subcellular labeling of dysferlin colocalizes with the developing T-tubule system. Furthermore, ultrastructural analysis of dysferlin-deficient muscle revealed primary T-tubule anomalies similar to those seen in caveolin-3-deficient muscle. These findings indicate that dysferlin is necessary for correct T-tubule formation, and dysferlin-deficient skeletal muscle is characterized by abnormally configured T-tubules.
Klinge
Lars
L
Institute of Human Genetics, International Centre for Life, University of Newcastle, Newcastle-upon-Tyne NE1 3BZ, UK.
Harris
John
J
Sewry
Caroline
C
Charlton
Richard
R
Anderson
Louise
L
Laval
Steve
S
Chiu
Yen-Hui
YH
Hornsey
Mark
M
Straub
Volker
V
Barresi
Rita
R
Lochmüller
Hanns
H
Bushby
Kate
K
D000818:Animals; D001706:Biopsy; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D000073939:Dysferlin; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009136:Muscular Dystrophies / Q000378:metabolism* / Q000473:pathology; D049288:Muscular Dystrophies, Limb-Girdle / Q000378:metabolism* / Q000473:pathology; D009154:Mutation / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012038:Regeneration; D012508:Sarcolemma / Q000378:metabolism* / Q000473:pathology
C114839:DYSF protein, human; C547052:Dysf protein, rat; D000073939:Dysferlin; D008565:Membrane Proteins; D009124:Muscle Proteins