PUBLICATION

Talin1 is required for cardiac Z-disk stabilization and endothelial integrity in zebrafish

Authors
Wu, Q., Zhang, J., Koh, W., Yu, Q., Zhu, X., Amsterdam, A., Davis, G.E., Arnaout, M.A., Xiong, J.W.
ID
ZDB-PUB-150828-8
Date
2015
Source
FASEB journal : official publication of the Federation of American Societies for Experimental Biology   29(12): 4989-5005 (Journal)
Registered Authors
Amsterdam, Adam, Xiong, Jing-Wei, Yu, Qingming, Zhang, Jiaojiao
Keywords
cardiac sarcomere, cardiovascular development, itgb1b, tln1
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Endothelium, Vascular/cytology*
  • Heart/embryology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Integrin beta1/genetics
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Sequence Homology, Amino Acid
  • Talin/chemistry
  • Talin/genetics
  • Talin/physiology*
  • Zebrafish/embryology
PubMed
26310270 Full text @ FASEB J.
Abstract
Talin (tln) binds and activates integrins to couple extracellular matrix-bound integrins to the cytoskeleton; however, its role in heart development is not well characterized. We identified the defective gene and the resulting cardiovascular phenotypes in zebrafish tln1(fl02k) mutants. The ethylnitrosourea-induced fl02k mutant showed heart failure, brain hemorrhage, and diminished cardiac and vessel lumens at 52 h post fertilization. Positional cloning revealed a nonsense mutation of tln1 in this mutant. tln1, but neither tln2 nor -2a, was dominantly expressed in the heart and vessels. Unlike tln1 and -2 in the mouse heart, the unique tln1 expression in the heart enabled us, for the first time, to determine the critical roles of Tln1 in the maintenance of cardiac sarcomeric Z-disks and endothelial/endocardial cell integrity, partly through regulating F-actin networks in zebrafish. The similar expression profiles of tln1 and integrin β1b (itgb1b) and synergistic function of the 2 genes revealed that itgb1b is a potential partner for tln1 in the stabilization of cardiac Z-disks and vessel lumens. Taken together, the results of this work suggest that Tln1-mediated Itgβ1b plays a crucial role in maintaining cardiac sarcomeric Z-disks and endothelial/endocardial cell integrity in zebrafish and may also help to gain molecular insights into congenital heart diseases.-Wu, Q., Zhang, J., Koh, W., Yu, Q., Zhu, X., Amsterdam, A., Davis, G. E., Arnaout, M. A., Xiong, J.-W. Talin1 is required for cardiac Z-disk stabilization and endothelial integrity in zebrafish.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes