ZFIN ID: ZDB-PUB-160310-11
Paxillin and Focal Adhesion Kinase (FAK) Regulate Cardiac Contractility in the Zebrafish Heart
Hirth, S., Bühler, A., Bührdel, J.B., Rudeck, S., Dahme, T., Rottbauer, W., Just, S.
Date: 2016
Source: PLoS One   11: e0150323 (Journal)
Registered Authors: Bühler, Anja, Bührdel, John, Dahme, Tillmann, Hirth, Sophia, Just, Steffen, Rottbauer, Wolfgang, Rudeck, Steven
Keywords: Embryos, Zebrafish, Heart failure, Heart, Focal adhesions, Cardiac ventricles, Messenger RNA, Protein kinase signaling cascade
MeSH Terms:
  • Animals
  • Focal Adhesion Protein-Tyrosine Kinases/genetics
  • Focal Adhesion Protein-Tyrosine Kinases/metabolism*
  • Gene Silencing
  • Heart Failure/genetics
  • Heart Failure/metabolism
  • Myocardial Contraction*
  • Myocardium/metabolism*
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/metabolism
  • Paxillin/genetics
  • Paxillin/metabolism*
  • Proteolysis
  • Vinculin/genetics
  • Vinculin/metabolism*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 26954676 Full text @ PLoS One
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ABSTRACT
An orchestrated interplay of adaptor and signaling proteins at mechano-sensitive sites is essential to maintain cardiac contractility and when defective leads to heart failure. We recently showed that Integrin-linked Kinase (ILK), ß-Parvin and PINCH form the IPP-complex to grant tuned Protein Kinase B (PKB) signaling in the heart. Loss of one of the IPP-complex components results in destabilization of the whole complex, defective PKB signaling and finally heart failure. Two components of IPP, ILK and ß-Parvin directly bind to Paxillin; however, the impact of this direct interaction on the maintenance of heart function is not known yet. Here, we show that targeted gene inactivation of Paxillin results in progressive decrease of cardiac contractility and heart failure in zebrafish without affecting IPP-complex stability and PKB phosphorylation. However, we found that Paxillin deficiency leads to the destabilization of its known binding partner Focal Adhesion Kinase (FAK) and vice versa resulting in degradation of Vinculin and thereby heart failure. Our findings highlight an essential role of Paxillin and FAK in controlling cardiac contractility via the recruitment of Vinculin to mechano-sensitive sites in cardiomyocytes.
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