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dc.contributor.authorHsieh, Fang-Chien_US
dc.contributor.authorLu, Yu-Fenen_US
dc.contributor.authorLiau, Ianen_US
dc.contributor.authorChen, Chien-Changen_US
dc.contributor.authorCheng, Chao-Minen_US
dc.contributor.authorHsiao, Chung-Deren_US
dc.contributor.authorHwang, Sheng-Ping L.en_US
dc.date.accessioned2018-08-21T05:53:40Z-
dc.date.available2018-08-21T05:53:40Z-
dc.date.issued2018-05-18en_US
dc.identifier.issn2045-2322en_US
dc.identifier.urihttp://dx.doi.org/10.1038/s41598-018-26110-3en_US
dc.identifier.urihttp://hdl.handle.net/11536/145000-
dc.description.abstractSarcomeric signaling complexes are important to sustain proper sarcomere structure and function, however, the mechanisms underlying these processes are not fully elucidated. In a gene trap experiment, we found that vascular cell adhesion protein 1 isoform X2 (VCAP1X2) mutant embryos displayed a dilated cardiomyopathy phenotype, including reduced cardiac contractility, enlarged ventricular chamber and thinned ventricular compact layer. Cardiomyocyte and epicardial cell proliferation was decreased in the mutant heart ventricle, as was the expression of pAKT and pERK. Contractile dysfunction in the mutant was caused by sarcomeric disorganization, including sparse myofilament, blurred Z-disc, and decreased gene expression for sarcomere modulators (smyd1b, mypn and fhl2 alpha), sarcomeric proteins (myh6, myh7, vmhcl and tnnt2 alpha) and calcium regulators (ryr2b and slc8a1 alpha). Treatment of PI3K activator restored Z-disc alignment while injection of smyd1b mRNA restored Z-disc alignment, contractile function and cardiomyocyte proliferation in ventricles of VCAP1X2 mutant embryos. Furthermore, injection of VCAP1X2 variant mRNA rescued all phenotypes, so long as two cytosolic tyrosines were left intact. Our results reveal two tyrosine residues located in the VCAP1X2 cytoplasmic domain are essential to regulate cardiac contractility and the proliferation of ventricular cardiomyocytes and epicardial cells through modulating pAKT and pERK expression levels.en_US
dc.language.isoen_USen_US
dc.titleZebrafish VCAP1X2 regulates cardiac contractility and proliferation of cardiomyocytes and epicardial cellsen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41598-018-26110-3en_US
dc.identifier.journalSCIENTIFIC REPORTSen_US
dc.citation.volume8en_US
dc.contributor.department應用化學系zh_TW
dc.contributor.department應用化學系分子科學碩博班zh_TW
dc.contributor.departmentDepartment of Applied Chemistryen_US
dc.contributor.departmentInstitute of Molecular scienceen_US
dc.identifier.wosnumberWOS:000432441400044en_US
Appears in Collections:Articles