Dysferlin, Annexin A1, and Mitsugumin 53 Are Upregulated in Muscular Dystrophy and Localize to Longitudinal Tubules of the T-System With Stretch

被引：80

作者：

Waddell, Leigh B. ^{[1
]}

Lemckert, Frances A. ^{[1
]}

Zheng, Xi F. ^{[1
]}

Tran, Jenny ^{[1
]}

Evesson, Frances J. ^{[1
]}

Hawkes, Joanne M. ^{[1
]}

Lek, Angela ^{[1
]}

Street, Neil E. ^{[1
,2
]}

Lin, Peihui ^{[3
]}

Clarke, Nigel F.

Landstrom, Andrew P. ^{[4
]}

Ackerman, Michael J. ^{[4
]}

Weisleder, Noah ^{[3
]}

Ma, Jianjie ^{[3
]}

North, Kathryn N. ^{[1
]}

Cooper, Sandra T. ^{[1
]}

机构：

[1] Univ Sydney, Childrens Hosp, Inst Neurosci & Muscle Res, Discipline Paediat & Child Hlth, Westmead, NSW 2145, Australia

[2] Childrens Hosp Westmead, Dept Anaesthesia, Sydney, NSW, Australia

[3] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Physiol & Biophys, Piscataway, NJ 08854 USA

[4] Mayo Clin, Coll Med, Mayo Med Sch, Dept Internal Med,Div Cardiovasc Dis, Rochester, MN USA

来源：

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY | 2011年 / 70卷 / 04期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

Annexin A1; Dysferlin; MG53; Membrane repair; Muscular dystrophy; Skeletal muscle; SKELETAL-MUSCLE FIBERS; MEMBRANE REPAIR; REVERSIBLE VACUOLATION; VESICLE FUSION; CAVEOLIN-3; MUTATIONS; MOUSE; MG53; FROG; PATHOGENESIS;

D O I：

10.1097/NEN.0b013e31821350b0

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

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.

引用

页码：302 / 313

页数：12