PUBLICATION

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

Authors
Hsieh, F.C., Lu, Y.F., Liau, I., Chen, C.C., Cheng, C.M., Hsiao, C.D., Hwang, S.L.
ID
ZDB-PUB-180520-2
Date
2018
Source
Scientific Reports   8: 7856 (Journal)
Registered Authors
Hsiao, Chung-Der, Hwang, Sheng-Ping L.
Keywords
none
MeSH Terms
  • Sodium-Calcium Exchanger/genetics
  • Sodium-Calcium Exchanger/metabolism
  • Myofibrils/metabolism
  • Sarcomeres/chemistry
  • Sarcomeres/physiology
  • Phosphorylation
  • Zebrafish/metabolism*
  • Calcium/metabolism
  • Heart Ventricles/metabolism
  • Myosin Heavy Chains/genetics
  • Myosin Heavy Chains/metabolism
  • Myocardial Contraction
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/metabolism
  • Cell Proliferation
  • Extracellular Signal-Regulated MAP Kinases/metabolism
  • Animals
  • Mutagenesis
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • Protein Isoforms/chemistry
  • Protein Isoforms/genetics
  • Protein Isoforms/metabolism
  • Vascular Cell Adhesion Molecule-1/chemistry
  • Vascular Cell Adhesion Molecule-1/genetics
  • Vascular Cell Adhesion Molecule-1/metabolism*
  • Proto-Oncogene Proteins c-akt/metabolism
(all 28)
PubMed
29777134 Full text @ Sci. Rep.
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 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.
Genes / Markers
Figures
Figure Gallery (10 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
icam3as31Gtstandard conditionsPrim-5
icam3as31Gtstandard conditionsLong-pec
icam3as31Gtstandard conditionsProtruding-mouth
icam3as31Gtstandard conditionsProtruding-mouth
icam3as31Gtstandard conditionsProtruding-mouth
icam3as31Gtstandard conditionsDay 5
icam3as31Gt; cy13Tgstandard conditionsDay 4
1 - 7 of 7
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
as31GtTransgenic Insertion
cy13TgTransgenic Insertion
    pd41TgTransgenic Insertion
      pd108TgTransgenic Insertion
        y1TgTransgenic Insertion
          1 - 5 of 5
          Show
          Human Disease / Model
          Human Disease Fish Conditions Evidence
          dilated cardiomyopathyicam3as31Gtstandard conditionsTAS
          1 - 1 of 1
          Show
          Sequence Targeting Reagents
          Target Reagent Reagent Type
          icam3MO1-icam3MRPHLNO
          1 - 1 of 1
          Show
          Fish
          Fish
          cy13Tg
          icam3as31Gt
          icam3as31Gt; cy13Tg
          icam3as31Gt; y1Tg
          pd108Tg; pd41Tg
          WT
          y1Tg
          1 - 7 of 7
          Show
          Antibodies
          No data available
          Orthology
          No data available
          Engineered Foreign Genes
          Marker Marker Type Name
          EGFPEFGEGFP
          GAL4EFGGAL4
          mCherryEFGmCherry
          NTREFGNTR
          1 - 4 of 4
          Show
          Mapping
          No data available
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          Citation
          Hsieh, F.C., Lu, Y.F., Liau, I., Chen, C.C., Cheng, C.M., Hsiao, C.D., Hwang, S.L. (2018) Zebrafish VCAP1X2 regulates cardiac contractility and proliferation of cardiomyocytes and epicardial cells. Scientific Reports. 8:7856.