McCullagh Karl J A, Edwards Ben, Poon Ellen, Lovering Richard M, Paulin Denise, Davies Kay E
MRC Functional Genetics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
Neuromuscul Disord. 2007 Dec;17(11-12):970-9. doi: 10.1016/j.nmd.2007.06.004. Epub 2007 Jul 12.
The intermediate filament-like protein syncoilin is a member of the dystrophin protein complex, and links the complex to the cytoskeleton through binding alpha-dystrobrevin and desmin in muscle. Here, we identify further sites of syncoilin location in normal muscle: at the perinuclear space, myotendinous junction, and enrichment in the sarcolemma and sarcoplasm of oxidative muscle fibers in mice. To understand the importance of the dystrophin protein complex-syncoilin-cytoskeletal link and its implication to disease, we analyzed syncoilin in mice null for alpha-dystrobrevin (adbn-/-) and desmin (des-/-). Syncoilin was upregulated in dystrophic muscles of adbn-/- mice, without alteration in its subcellular location. In des-/- mice, syncoilin was severely reduced in skeletal muscle; lost from sarcomeric Z-lines and neuromuscular junctions, and redistributed from the sub-sarcolemmal cytoskeleton to the cytoplasm. The data show that absence of alpha-dystrobrevin or desmin leads to dynamic changes in syncoilin that may compensate for, or participate in, different muscle myopathies.
中间丝样蛋白伴肌动蛋白是肌营养不良蛋白复合体的成员，在肌肉中通过结合α- dystrobrevin和结蛋白将该复合体与细胞骨架相连。在此，我们确定了伴肌动蛋白在正常肌肉中的其他定位位点：在核周间隙、肌-腱连接部位以及小鼠氧化型肌纤维的肌膜和肌浆中富集。为了理解肌营养不良蛋白复合体-伴肌动蛋白-细胞骨架连接的重要性及其与疾病的关联，我们分析了α- dystrobrevin基因敲除（adbn-/-）和结蛋白基因敲除（des-/-）小鼠中的伴肌动蛋白。在adbn-/-小鼠的营养不良肌肉中，伴肌动蛋白上调，其亚细胞定位未改变。在des-/-小鼠中，骨骼肌中的伴肌动蛋白严重减少；从肌节Z线和神经肌肉接头处消失，并从肌膜下细胞骨架重新分布到细胞质中。数据表明，α- dystrobrevin或结蛋白的缺失导致伴肌动蛋白的动态变化，这可能补偿或参与不同的肌肉肌病。
