Zebrafish VCAP1X2 regulates cardiac contractility and proliferation of cardiomyocytes and epicardial cells

Scientific Reports
Fang-Chi HsiehSheng-Ping L Hwang

Abstract

Sarcomeric 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 fhl2a), sarcomeric proteins (myh6, myh7, vmhcl and tnnt2a) and calcium regulators (ryr2b and slc8a1a). 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 lo...Continue Reading

References

Feb 16, 1995·Nature·T Pawson
Jul 1, 1995·Developmental Dynamics : an Official Publication of the American Association of Anatomists·C B KimmelT F Schilling
Dec 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·A L LazaarS K Das
Oct 2, 2003·Current Opinion in Cell Biology·Neta Ilan, Joseph A Madri
Dec 17, 2003·The Journal of Biological Chemistry·Belinda BullardWolfgang A Linke
May 1, 2004·Circulation Research·Karen A LapidosElizabeth M McNally
Jul 9, 2004·Developmental Cell·Koichi KawakamiMasayoshi Mishina
Aug 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Alistair J WattStephen A Duncan
Mar 30, 2006·BioTechniques·C Geoffrey Burns, Calum A MacRae
May 26, 2007·Circulation Research·Gregory E HanniganShoukat Dedhar
Aug 25, 2007·Nature Reviews. Immunology·Klaus LeySussan Nourshargh
Nov 1, 2008·Cardiovascular Research·Monte S WillisCam Patterson
Mar 3, 2009·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Yi-Hua ChenSheng-Ping L Hwang
Apr 24, 2010·Circulation Research·Jiandong Liu, Didier Y R Stainier
Nov 16, 2010·Annual Review of Pathology·William A Muller
Jan 25, 2011·The Journal of Biological Chemistry·Derk Frank, Norbert Frey
May 10, 2011·Methods in Cell Biology·Daniel Verduzco, James F Amatruda
May 24, 2011·Cardiovascular Research·Jeroen Bakkers
Jul 16, 2011·The Journal of Biological Chemistry·Ashley J WaardenbergJulie R McMullen
Aug 20, 2011·Journal of Cell Science·Steffen JustWolfgang Rottbauer
Oct 27, 2011·Journal of Biomedicine & Biotechnology·Ralph KnöllMax Lab
Jan 10, 2012·Methods in Molecular Biology·Tiffany HoageXiaolei Xu
Jan 20, 2012·Journal of Visualized Experiments : JoVE·Jingchun Yang, Xiaolei Xu
Oct 30, 2012·Circulation Research·Oghenerukevwe OdieteDouglas B Sawyer
Jan 3, 2013·The Journal of Clinical Investigation·Elizabeth M McNallyMegan J Puckelwartz
Jan 30, 2013·Proceedings of the National Academy of Sciences of the United States of America·Run FanBarry M Gumbiner
Aug 1, 2013·Nature Reviews. Cardiology·Ray E HershbergerAna Morales
May 1, 2011·Progress in Pediatric Cardiology·Angela K PeterJu Chen
Sep 27, 2013·Molecular Biology of the Cell·Huiqing LiShao Jun Du
Jan 15, 2015·Circulation. Cardiovascular Genetics·Yu-Huan ShihXiaolei Xu
Mar 7, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Yiqing YangMark L Kahn

❮ Previous
Next ❯

Citations

Aug 9, 2020·Thyroid : Official Journal of the American Thyroid Association·Cho Rong HanSheue-Yann Cheng
Jan 8, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Martin Ezeani, Sandeep Prabhu

❮ Previous
Next ❯

Methods Mentioned

BETA
gene trap
gene
transgenic
Transmission electron microscopy
reverse-transcription PCR
nuclear translocation
immunoprecipitation
fluorescence microscopy
electrophoresis

Software Mentioned

Imaris
Image J
Excel
R
BLAST

Related Concepts

Related Feeds

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.