Myosin-18B Regulates Higher-Order Organization of the Cardiac Sarcomere through Thin Filament Cross-Linking and Thick Filament Dynamics.

Autor:	Latham SL; Institute for Biophysical Chemistry, Hannover Medical School, Hannover 30625, Germany; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St Vincent's Hospital Clinical School, UNSW Sydney, NSW 2052, Australia., Weiß N; Institute for Biophysical Chemistry, Hannover Medical School, Hannover 30625, Germany., Schwanke K; Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, REBIRTH-Cluster of Excellence, Hannover Medical School, Hannover 30625, Germany., Thiel C; Institute for Biophysical Chemistry, Hannover Medical School, Hannover 30625, Germany., Croucher DR; The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia; St Vincent's Hospital Clinical School, UNSW Sydney, NSW 2052, Australia., Zweigerdt R; Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, REBIRTH-Cluster of Excellence, Hannover Medical School, Hannover 30625, Germany., Manstein DJ; Institute for Biophysical Chemistry, Hannover Medical School, Hannover 30625, Germany., Taft MH; Institute for Biophysical Chemistry, Hannover Medical School, Hannover 30625, Germany. Electronic address: taft.manuel@mh-hannover.de.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2020 Sep 01; Vol. 32 (9), pp. 108090.
DOI:	10.1016/j.celrep.2020.108090
Abstrakt:	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. Competing Interests: Declaration of Interests The authors declare no competing interests. (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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