ZFIN ID: ZDB-PUB-151114-7
The Effects of Hsp90α1 Mutations on Myosin Thick Filament Organization
He, Q., Liu, K., Tian, Z., Du, S.J.
Date: 2015
Source: PLoS One 10: e0142573 (Journal)
Registered Authors: Du, Shao Jun (Jim)
Keywords: Zebrafish, Embryos, Myosins, Phosphorylation, Acetylation, Adenosine triphosphatase, DNA methylation, Skeletal muscles
MeSH Terms: Acetylation; Adenosine Triphosphate/metabolism; Animals; Animals, Genetically Modified; Binding Sites/genetics (all 23) expand
PubMed: 26562659 Full text @ PLoS One
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ABSTRACT
Heat shock protein 90α plays a key role in myosin folding and thick filament assembly in muscle cells. To assess the structure and function of Hsp90α and its potential regulation by post-translational modification, we developed a combined knockdown and rescue assay in zebrafish embryos to systematically analyze the effects of various mutations on Hsp90α function in myosin thick filament organization. DNA constructs expressing the Hsp90α1 mutants with altered putative ATP binding, phosphorylation, acetylation or methylation sites were co-injected with Hsp90α1 specific morpholino into zebrafish embryos. Myosin thick filament organization was analyzed in skeletal muscles of the injected embryos by immunostaining. The results showed that mutating the conserved D90 residue in the Hsp90α1 ATP binding domain abolished its function in thick filament organization. In addition, phosphorylation mimicking mutations of T33D, T33E and T87E compromised Hsp90α1 function in myosin thick filament organization. Similarly, K287Q acetylation mimicking mutation repressed Hsp90α1 function in myosin thick filament organization. In contrast, K206R and K608R hypomethylation mimicking mutations had not effect on Hsp90α1 function in thick filament organization. Given that T33 and T87 are highly conserved residues involved post-translational modification (PTM) in yeast, mouse and human Hsp90 proteins, data from this study could indicate that Hsp90α1 function in myosin thick filament organization is potentially regulated by PTMs involving phosphorylation and acetylation.
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