Myomesin is part of an integrity pathway that responds to sarcomere damage and disease

Abstract

The structure and function of the sarcomere of striated muscle is well studied but the steps of sarcomere assembly and maintenance remain under-characterized. With the aid of chaperones and factors of the protein quality control system, muscle proteins can be folded and assembled into the contractile apparatus of the sarcomere. When sarcomere assembly is incomplete or the sarcomere becomes damaged, suites of chaperones and maintenance factors respond to repair the sarcomere. Here we show evidence of the importance of the M-line proteins, specifically myomesin, in the monitoring of sarcomere assembly and integrity in previously characterized zebrafish muscle mutants. We show that myomesin is one of the last proteins to be incorporated into the assembling sarcomere, and that in skeletal muscle, its incorporation requires connections with both titin and myosin. In diseased zebrafish sarcomeres, myomesin1a shows an early increase of gene expression, hours before chaperones respond to damaged muscle. We found that myomesin expression is also more specific to sarcomere damage than muscle creatine kinase, and our results and others support the use of myomesin assays as an early, specific, method of detecting muscle damage.

Pathogenic Variants in the Myosin Chaperone UNC-45B Cause Progressive Myopathy with Eccentric Cores

“…Immunofluorescence localization studies were performed with myomesin, a major structural protein of the M-line, and a-actinin, a Z-line protein, as markers. 27 Whereas, in control muscle, UNC-45B localized to the A-band around the M-line as expected, in affected individuals, there appears to be a loss of the residual UNC-45B at the M-line, suggestive of mislocalization away from the A-band to the Z-disk (Figures 3A and 3B). The specificity of the UNC-45B antibody was confirmed in control muscle (Figure S2).…”

The Potential Role of MYOM1 and ATGL Genes in Pig Production Improvement

“…Moreover, the disruption of each protein (including myomesin 1) involved in M-line structure can result in the degeneration of the sarcomere (Fukuzawa et al, 2008;Prill et al, 2019). In the present research, the significant association of c.2539G>A polymorphism with lean meat characteristics was detected.…”

CRISPR gene editing in pluripotent stem cells reveals the function of MBNL proteins during humanin vitromyogenesis

“…Among the list of downregulated genes identified in DKO hiPSC-derived myotubes, we highlighted two interesting candidates for further explorations ( Fig. 6F ): TCAP (also known as Telethonin) plays an essential role in the sarcomeric assembly by anchoring Titin in the Z-disk of the sarcomere ( 27 ) and is known to be involved in limb-girdle muscular dystrophy 2G ( 28 ); MYOM1 is a constituent of the sarcomeric M band and plays an important role in sarcomere assembly and integrity ( 29 ). Interestingly, MYOM1 is found mis-spliced in muscular biopsies from DM1 patients ( 30 ), and this splicing defect could be caused by the downregulation of MBNL proteins ( 31 ).…”