Unité de Morphologie Neuromusculaire, and the Centre de Référence Neuromusculaire Paris-Est, Institut de Myologie, Groupe Hospitalier Pitié-Salpêtrière, AP-HP, Paris, France
Am J Pathol. 2010 Jun;176(6):2901-10. doi: 10.2353/ajpath.2010.090663. Epub 2010 Apr 15.
DNAJB2, a co-chaperone regulator of Hsp70 that is expressed principally in the nervous system, has been recently reported to be up-regulated in human skeletal muscle during its recovery from damage. Here we identified DNAJB2 expression in regenerating fibers in skeletal muscles of the dystrophic mdx mouse and patients with Duchenne muscular dystrophy. Surprisingly, in both dystrophic and control mice and patients, DNAJB2 was also expressed in non-regenerating fibers at the postsynaptic side of the neuromuscular junction. DNAJB2 functions as an adaptor molecule for the evacuation and degradation of proteins through the ubiquitin-proteasome system, and overexpression of DNAJB2 in models of the neurodegenerative disease spinobulbar muscular atrophy was shown to result in the reduction of protein inclusions. We therefore studied the possible relation of DNAJB2 expression to protein inclusion formation in skeletal muscle in biopsies of several muscle pathologies associated with protein aggregation and found in all of them a strong immunoreactivity with anti-DNAJB2 in aggregates and vacuoles. We conclude that DNAJB2 is expressed in mouse and human skeletal muscle at the neuromuscular junction of normal fibers, in the cytoplasm and membrane of regenerating fibers, and in protein aggregates and vacuoles in protein aggregate myopathies. Therefore, we propose a role for DNAJB2 in protein turnover processes in skeletal muscle.
DNAJB2 是一种 HSP70 的共伴侣调节剂，主要在神经系统中表达，最近有报道称，在人类骨骼肌从损伤中恢复时，其表达水平上调。在这里，我们鉴定了 DNAJB2 在肌营养不良症 mdx 小鼠和杜氏肌营养不良症患者的骨骼肌再生纤维中的表达。令人惊讶的是，在两种营养不良症和对照小鼠和患者中，DNAJB2 也在神经肌肉接头的突触后侧的非再生纤维中表达。DNAJB2 作为一种衔接分子，通过泛素-蛋白酶体系统促进蛋白质的清除和降解，在神经退行性疾病痉挛性延髓麻痹的模型中过表达 DNAJB2 导致蛋白质包涵体减少。因此，我们研究了 DNAJB2 表达与几种与蛋白质聚集相关的肌肉病理活检中骨骼肌中蛋白质包涵体形成的可能关系，在所有这些病理中，抗 DNAJB2 在包涵体和空泡中均有强烈的免疫反应性。我们得出结论，DNAJB2 在正常纤维的神经肌肉接头、再生纤维的细胞质和膜中以及在蛋白质聚集性肌病中的蛋白质聚集体和空泡中表达。因此，我们提出 DNAJB2 在骨骼肌蛋白质周转过程中的作用。
