title: 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 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.
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Liang-Yi
authors.initials: LY
authors.lastname: Juo
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Wern-Chir
authors.initials: WC
authors.lastname: Liao
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Yen-Ling
authors.initials: YL
authors.lastname: Shih
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
authors.forename: Bih-Ying
authors.initials: BY
authors.lastname: Yang
authors.affiliation: Department of Neurology, Buddhist Tzu Chi General Hospital and Buddhist Tzu Chi University, Hualien 970, Taiwan.
authors.forename: An-Bang
authors.initials: AB
authors.lastname: Liu
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 112, Taiwan Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan yyan@ibms.sinica.edu.tw.
authors.forename: Yu-Ting
authors.identifier: http://orcid.org/0000-0002-9559-706X
authors.initials: YT
authors.lastname: Yan
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003964:Diaphragm / Q000473:pathology*; D019281:Dimerization; D005355:Fibrosis; D064448:Filamins / Q000378:metabolism*; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024510:Muscle Development / Q000235:genetics; D018482:Muscle, Skeletal / Q000502:physiology*; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport / Q000235:genetics; D012119:Respiration / Q000235:genetics; D049031:Sarcoglycans / Q000378:metabolism
chemical_list: D064448:Filamins; D055551:HSP27 Heat-Shock Proteins; C000613262:HSPB7 protein, mouse; D049031:Sarcoglycans
keywords: FLNC; HSPB7; Myopathy