Dual function of the UNC-45b chaperone with myosin and GATA4 in cardiac development.

Journal of Cell Science
Daisi ChenH F Epstein

Abstract

Cardiac development requires interplay between the regulation of gene expression and the assembly of functional sarcomeric proteins. We report that UNC-45b recessive loss-of-function mutations in C3H and C57BL/6 inbred mouse strains cause arrest of cardiac morphogenesis at the formation of right heart structures and failure of contractile function. Wild-type C3H and C57BL/6 embryos at the same stage, E9.5, form actively contracting right and left atria and ventricles. The known interactions of UNC-45b as a molecular chaperone are consistent with diminished accumulation of the sarcomeric myosins, but not their mRNAs, and the resulting decreased contraction of homozygous mutant embryonic hearts. The novel finding that GATA4 accumulation is similarly decreased at the protein but not mRNA levels is also consistent with the function of UNC-45b as a chaperone. The mRNAs of known downstream targets of GATA4 during secondary cardiac field development, the cardiogenic factors Hand1, Hand2 and Nkx-2.5, are also decreased, consistent with the reduced GATA4 protein accumulation. Direct binding studies show that the UNC-45b chaperone forms physical complexes with both the alpha and beta cardiac myosins and the cardiogenic transcription fact...Continue Reading

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Citations

Sep 23, 2014·FEBS Letters·Paul NichollsAndres F Oberhauser
Nov 14, 2012·Trends in Cardiovascular Medicine·Henry F Epstein, Guy M Benian
Aug 16, 2014·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Daniel A SmithSanford I Bernstein
Jun 14, 2016·Genesis : the Journal of Genetics and Development·Steven RudeckSteffen Just
Jan 13, 2018·FEBS Open Bio·Paul J BujalowskiAndres F Oberhauser
Nov 21, 2020·American Journal of Human Genetics·Sandra DonkervoortCarsten G Bönnemann

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