Myosin-18B regulates higher-order organization of the cardiac sarcomere through thin filament cross-linking and thick filament dynamics
MYO18B loss-of-function mutations and depletion significantly compromise the structural integrity of striated muscle sarcomeres. The molecular function of the encoded protein, myosin-18B (M18B), within the developing muscle is unknown. Here, we demonstrate that recombinant M18B lacks motor ATPase activity and harbors previously uncharacterized N-terminal actin-binding domains, properties that make M18B an efficient actin cross-linker and molecular brake capable of regulating muscle myosin-2 contractile forces. Spatiotemporal analysis of M18B throughout cardiomyogenesis and myofibrillogenesis reveals that this structural myosin undergoes nuclear-cytoplasmic redistribution during myogenic differentiation, where its incorporation within muscle stress fibers coincides with actin striation onset. Furthermore, this analysis shows that M18B is directly integrated within the muscle myosin thick filament during myofibril maturation. Altogether, our data suggest that M18B has evolved specific biochemical properties that allow it to define and maintain sarcomeric organization from within the thick filament via its dual actin cross-linking and motor modulating capabilities.
|Authors||Latham, S. L.; Weiss, N.; Schwanke, K.; Thiel, C.; Croucher, D. R.; Zweigerdt, R.; Manstein, D. J.; Taft, M. H.|
|Responsible Garvan Author|
|Publisher Name||Cell Reports|
|URL link to publisher's version||https://www.ncbi.nlm.nih.gov/pubmed/32877672|