Howman Emily V, Sullivan Nicky, Poon Ellen P, Britton Joanna E, Hilton-Jones David, Davies Kay E
Department of Human Anatomy and Genetics, University of Oxford, South Parks Road, OX13QX, Oxford, UK.
Neuromuscul Disord. 2003 Jan;13(1):42-8. doi: 10.1016/s0960-8966(02)00181-5.
We have recently shown that syncoilin interacts with desmin in skeletal muscle and has a role in attaching and organising desmin filaments to the Z-lines. We have analysed patients with desmin accumulation and have found that syncoilin is both upregulated at the sarcolemma and aggregates with desmin indicating the presence of two distinct protein populations. Additional dystrophin-associated protein complex components also accumulate. The striking finding was that alpha-dystrobrevin-1 and neuronal nitric oxide synthase (nNOS) are almost completely lost from the membrane of these patients indicating that the myopathy may result from both the abnormal accumulation of proteins and an increase in ischaemic injury due to the loss of nNOS. We speculate that the loss of alpha-dystrobrevin from the membrane, and subsequent loss of nNOS, is due to the alpha-dystrobrevin-syncoilin-desmin interaction.
我们最近发现，伴肌动蛋白在骨骼肌中与结蛋白相互作用，并且在将结蛋白丝附着并组织到Z线中发挥作用。我们分析了有结蛋白积聚的患者，发现伴肌动蛋白在肌膜处上调，并且与结蛋白聚集，这表明存在两种不同的蛋白质群体。其他肌营养不良蛋白相关蛋白复合物成分也会积聚。引人注目的发现是，α- dystrobrevin -1和神经元型一氧化氮合酶（nNOS）在这些患者的膜上几乎完全缺失，这表明肌病可能是由于蛋白质的异常积聚以及由于nNOS缺失导致的缺血性损伤增加所致。我们推测，α- dystrobrevin从膜上的缺失以及随后nNOS的缺失，是由于α- dystrobrevin -伴肌动蛋白-结蛋白的相互作用。
