ZFIN ID: ZDB-PUB-160312-7
Rac1-PAK2 pathway is essential for zebrafish heart regeneration
Peng, X., He, Q., Li, G., Ma, J., Zhong, T.P.
Date: 2016
Source: Biochemical and Biophysical Research Communications   472(4): 637-42 (Journal)
Registered Authors: Zhong, Tao P.
Keywords: Cardiovascular, Cdc42, Heart regeneration, PAK2, PAK4, Rac1, Zebrafish
MeSH Terms:
  • Animals
  • Enzyme Activation
  • Heart/physiology*
  • Heart Injuries/metabolism
  • Heart Injuries/pathology
  • Myocardium/metabolism
  • Myocardium/pathology
  • Myocytes, Cardiac/cytology
  • Myocytes, Cardiac/metabolism
  • Myocytes, Cardiac/pathology
  • Regeneration*
  • Signal Transduction*
  • Zebrafish/physiology*
  • Zebrafish Proteins/metabolism*
  • cdc42 GTP-Binding Protein/metabolism
  • p21-Activated Kinases/metabolism*
  • rac1 GTP-Binding Protein/metabolism*
PubMed: 26966072 Full text @ Biochem. Biophys. Res. Commun.
P-21 activated kinases, or PAKs, are serine-threonine kinases that play important roles in diverse heart functions include heart development, cardiovascular development and function in a range of models; however, the mechanisms by which PAKs mediate heart regeneration are unknown. Here, we demonstrate that PAK2 and PAK4 expression is induced in cardiomyocytes and vessels, respectively, following zebrafish heart injury. Inhibition of PAK2 and PAK4 using a specific small molecule inhibitor impedes cardiomyocyte proliferation/dedifferentiation and cardiovascular regeneration, respectively. Cdc42 is specifically expressed in the ventricle and may function upstream of PAK2 but not PAK4. Our results indicate that PAKs play a key role in heart regeneration.