title: Rac1-PAK2 pathway is essential for zebrafish heart regeneration.
abstract: 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 under normal conditions and that cardiomyocyte proliferentation during heart regeneration relies on Rac1-mediated activation of Pak2. Our results indicate that PAKs play a key role in heart regeneration.
authors.affiliation: State Key Laboratory of Genetic Engineering, Department of Genetics, School of Life Sciences, Fudan University, Shanghai 201203, China.
authors.forename: Xiangwen
authors.initials: X
authors.lastname: Peng
authors.affiliation: Center for Reproduction and Genetics, Suzhou Municipal Hospital, Jiangsu 215002, China.
authors.forename: Quanze
authors.initials: Q
authors.lastname: He
authors.affiliation: State Key Laboratory of Genetic Engineering, Department of Genetics, School of Life Sciences, Fudan University, Shanghai 201203, China.
authors.forename: Guobao
authors.initials: G
authors.lastname: Li
authors.affiliation: State Key Laboratory of Genetic Engineering, Department of Genetics, School of Life Sciences, Fudan University, Shanghai 201203, China.
authors.forename: Jinmin
authors.initials: J
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Genetic Engineering, Department of Genetics, School of Life Sciences, Fudan University, Shanghai 201203, China; Department of Medicine, Vanderbilt University School of Medicine, TN 37232, USA. Electronic address: taozhongfudan@yahoo.com.
authors.forename: Tao P
authors.initials: TP
authors.lastname: Zhong
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D006321:Heart / Q000502:physiology*; D006335:Heart Injuries / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D012038:Regeneration; D015398:Signal Transduction; D015027:Zebrafish / Q000502:physiology*; D029961:Zebrafish Proteins / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D054462:p21-Activated Kinases / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D029961:Zebrafish Proteins; C582243:rac1a protein, zebrafish; C582412:PAK4 protein, zebrafish; D054462:p21-Activated Kinases; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein
keywords: Cardiovascular; Cdc42; Heart regeneration; PAK2; PAK4; Rac1; Zebrafish