Dysferlin, annexin A1, and mitsugumin 53 are upregulated in muscular dystrophy and localize to longitudinal tubules of the T-system with stretch.
Dysferlin, annexin A1, and mitsugumin 53 are upregulated in muscular dystrophy and localize to longitudinal tubules of the T-system with stretch.
复制标题
Dysferlin、膜联蛋白 A1 和 mitsugumin 53 在肌营养不良症中表达上调，并定位于具有拉伸作用的 T 系统纵向小管。
DOI：
10.1097/nen.0b013e31821350b0
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发表时间：
2011-04
影响因子：
3.2
通讯作者：
Cooper ST
中科院分区：
文献类型：
--
作者：
Waddell LB;Lemckert FA;Zheng XF;Tran J;Evesson FJ;Hawkes JM;Lek A;Street NE;Lin P;Clarke NF;Landstrom AP;Ackerman MJ;Weisleder N;Ma J;North KN;Cooper ST
Mutations in dysferlin cause an inherited muscular dystrophy due to 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). MG53 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. MG53 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 labelling 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.
