Juo Liang-Yi, Liao Wern-Chir, Shih Yen-Ling, Yang Bih-Ying, Liu An-Bang, Yan Yu-Ting
Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
J Cell Sci. 2016 Apr 15;129(8):1661-70. doi: 10.1242/jcs.179887. Epub 2016 Feb 29.
HSPB7 belongs to the small heat-shock protein (sHSP) family, and its expression is restricted to cardiac and skeletal muscles from embryonic stages to adulthood. Here, we found that skeletal-muscle-specific ablation of the HspB7 does not affect myogenesis during embryonic stages to postnatal day 1 (P1), but causes subsequent postnatal death owing to a respiration defect, with progressive myopathy phenotypes in the diaphragm. Deficiency of HSPB7 in the diaphragm muscle resulted in muscle fibrosis, sarcomere disarray and sarcolemma integrity loss. We identified dimerized filamin C (FLNC) as an interacting partner of HSPB7. Immunofluorescence studies demonstrated that the aggregation and mislocalization of FLNC occurred in the muscle of HspB7 mutant adult mice. Furthermore, the components of dystrophin glycoprotein complex, γ- and δ-sarcoglycan, but not dystrophin, were abnormally upregulated and mislocalized in HSPB7 mutant muscle. Collectively, our findings suggest that HSPB7 is essential for maintaining muscle integrity, which is achieved through its interaction with FLNC, in order to prevent the occurrence and progression of myopathy.
HSPB7属于小热休克蛋白（sHSP）家族，其表达从胚胎期到成年期都局限于心肌和骨骼肌。在此，我们发现骨骼肌特异性敲除HspB7在胚胎期到出生后第1天（P1）不影响肌发生，但由于呼吸缺陷导致随后的出生后死亡，膈肌出现进行性肌病表型。膈肌中HSPB7的缺乏导致肌肉纤维化、肌节紊乱和肌膜完整性丧失。我们确定二聚化的细丝蛋白C（FLNC）是HSPB7的相互作用伴侣。免疫荧光研究表明，FLNC的聚集和定位错误发生在HspB7突变成年小鼠的肌肉中。此外，抗肌萎缩蛋白糖蛋白复合体的成分γ-和δ-肌聚糖，而非抗肌萎缩蛋白，在HSPB7突变肌肉中异常上调且定位错误。总的来说，我们的研究结果表明，HSPB7通过与FLNC相互作用对于维持肌肉完整性至关重要，以防止肌病的发生和发展。
