HSPB7 interacts with dimerized FLNC and its absence results in progressive myopathy in skeletal muscles

Abstract

HSPB7 belongs to the small heat shock protein (sHSP) family and restrictedly expresses in cardiac and skeletal muscles from embryonic stages to adulthood. Skeletal muscle-specific ablation of the HspB7 does not affect myogenesis during embryonic stages to postnatal day 1 (P1), but causes subsequent postnatal death by a respiration defect with progressive myopathy phenotypes in the diaphragm. The deficiency of HSPB7 in the diaphragm muscle results 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 were occurred in the muscle of HspB7 mutant adult mice. Furthermore, the components of dystrophin glycoprotein complex, γ- and δ-sarcoglycan but not dystrophin, are abnormally upregulated and mislocalized at HSPB7 mutant muscle. Collectively, our findings suggest that HSPB7 plays a functional role essential for maintaining muscle integrity by interaction with FLNC to prevent the occurrence and progression of myopathy.