HSPB7 interacts with dimerized FLNC and its absence results in progressive myopathy in skeletal muscles.
HSPB7 interacts with dimerized FLNC and its absence results in progressive myopathy in skeletal muscles.
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DOI：
10.1242/jcs.179887
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发表时间：
2016-04-15
影响因子：
4
通讯作者：
Yan YT
中科院分区：
文献类型：
--
作者：
Juo LY;Liao WC;Shih YL;Yang BY;Liu AB;Yan YT
HSPB 7属于小热休克蛋白（sHSP）家族，其表达仅限于胚胎期至成年期的心肌和骨骼肌。在这里，我们发现HspB 7的腹肌特异性消融不影响胚胎期至出生后第1天（P1）的肌发生，但由于呼吸缺陷导致随后的出生后死亡，膈肌中有进行性肌病表型。HSPB 7缺乏可导致膈肌纤维化、肌节排列紊乱和肌膜完整性丧失。我们确定了二聚细丝蛋白C（FLNC）作为热休克蛋白B7的相互作用伙伴。免疫荧光研究表明，FLNC的聚集和错误定位发生在HspB 7突变的成年小鼠的肌肉。此外，肌营养不良蛋白糖蛋白复合物的组分，γ-和δ-肌聚糖，而不是肌营养不良蛋白，在HSPB 7突变肌肉中异常上调和错误定位。总的来说，我们的研究结果表明，HSPB 7对于维持肌肉完整性至关重要，这是通过其与FLNC的相互作用来实现的，以防止肌病的发生和进展。HSPB 7在维持肌肉完整性方面起着至关重要的作用，可能是通过稳定FLNC的功能。
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. Highlighted Article: HSPB7 plays a crucial role in the maintenance of the muscle integrity, possibly through stabilizing the function of FLNC.