Dysferlin, annexin A1, and mitsugumin 53 are upregulated in muscular dystrophy and localize to longitudinal tubules of the T-system with stretch.
Abstract
Mutations in dysferlin cause an inherited muscular dystrophy because of defective
membrane repair. Three interacting partners of dysferlin are also implicated in membrane
resealing: caveolin-3 (in limb girdle muscular dystrophy type 1C), annexin A1, and
the newly identified protein mitsugumin 53 (MG53). Mitsugumin 53 accumulates at sites
of membrane damage, and MG53-knockout mice display a progressive muscular dystrophy.
This study explored the expression and localization of MG53 in human skeletal muscle,
how membrane repair proteins are modulated in various forms of muscular dystrophy,
and whether MG53 is a primary cause of human muscle disease. Mitsugumin 53 showed
variable sarcolemmal and/or cytoplasmic immunolabeling in control human muscle and
elevated levels in dystrophic patients. No pathogenic MG53 mutations were identified
in 50 muscular dystrophy patients, suggesting that MG53 is unlikely to be a common
cause of muscular dystrophy in Australia. Western blot analysis confirmed upregulation
of MG53, as well as of dysferlin, annexin A1, and caveolin-3 to different degrees,
in different muscular dystrophies. Importantly, MG53, annexin A1, and dysferlin localize
to the t-tubule network and show enriched labeling at longitudinal tubules of the
t-system in overstretch. Our results suggest that longitudinal tubules of the t-system
may represent sites of physiological membrane damage targeted by this membrane repair
complex.
Type
Journal articleSubject
Muscle, SkeletalSarcolemma
Cytoplasm
Microtubules
Humans
Muscular Dystrophies, Limb-Girdle
Carrier Proteins
Annexin A1
Muscle Proteins
Membrane Proteins
DNA
Microscopy, Confocal
Biopsy
Blotting, Western
Immunohistochemistry
Physical Stimulation
Up-Regulation
Adolescent
Adult
Aged
Middle Aged
Child
Child, Preschool
Infant
Young Adult
Dysferlin
Permalink
https://hdl.handle.net/10161/20328Published Version (Please cite this version)
10.1097/NEN.0b013e31821350b0Publication Info
Waddell, LB; Lemckert, FA; Zheng, XF; Tran, J; Evesson, FJ; Hawkes, JM; ... Cooper,
ST (2011). Dysferlin, annexin A1, and mitsugumin 53 are upregulated in muscular dystrophy and
localize to longitudinal tubules of the T-system with stretch. Journal of neuropathology and experimental neurology, 70(4). pp. 302-313. 10.1097/NEN.0b013e31821350b0. Retrieved from https://hdl.handle.net/10161/20328.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
Collections
More Info
Show full item recordScholars@Duke
Andrew Paul Landstrom
Associate Professor of Pediatrics
Dr. Landstrom is a physician scientist who specializes in the care of children and
young adults with arrhythmias, heritable cardiovascular diseases, and sudden unexplained
death syndromes. As a clinician, he is trained in pediatric cardiology with a focus
on arrhythmias and genetic diseases of the heart. He specializes in caring for patients
with heritable arrhythmia (channelopathies) such as long QT syndrome, Brugada syndrome,
catecholaminergic polymorphic ventricular tachycardia,

Articles written by Duke faculty are made available through the campus open access policy. For more information see: Duke Open Access Policy
Rights for Collection: Scholarly Articles
Works are deposited here by their authors, and represent their research and opinions, not that of Duke University. Some materials and descriptions may include offensive content. More info