scholarly journals A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart

2007 ◽  
Vol 117 (10) ◽  
pp. 2812-2824 ◽  
Author(s):  
Osamu Seguchi ◽  
Seiji Takashima ◽  
Satoru Yamazaki ◽  
Masanori Asakura ◽  
Yoshihiro Asano ◽  
...  
Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Osamu Seguchi ◽  
Seiji Takashima ◽  
Satoru Yamazaki ◽  
Masanori Asakura ◽  
Yoshihiro Asano ◽  
...  

Background Cardiomyocytes mainly consist of sarcomere structure and marked sarcomere disorganization is a well-documented characteristic of cardiomyocytes in the failing myocardium. Among several constituents of sarcomeres, myosin regulatory light chain 2 (MLC2v) affects physiological cardiac sarcomere formation and heart development through its phosphorylation. Exact upstream kinase of MLC2v in cardiomyocytes however, have not been elucidated so far. Mathods and Results We identified a novel cardiac-specific gene whose expression was upregulated in failing myocardium and was also correlated with the values of pulmonary arterial pressure of each patient. This gene has kinase domain and MLC2v was identified as a putative substrate by in vitro kinase reaction using mouse heart extracts and recombinant protein of this gene. Therefore, we termed this novel gene as a cardiac-specific myosin light chain kinase (cardiac-MLCK, gene symbol: MYLK3 ). To further investigate the function of cardiac-MLCK, we targeted cardiac-MLCK using specific siRNAs in cultured neonatal rat cardiomyocytes. Reduced expression of cardiac-MLCK caused the impairment of sarcomere reassembly on epinephrine treatment. Also knockdown of cardiac-MLCK expression in zebrafish embryos using specific morpholino antisense oligonucleotides led to dilation of the cardiac ventricle with incomplete sarcomere formation. We also analyzed the nature of cardiac-MLCK and MLC2v in mouse models of heart failure. Expression levels of cardiac-MLCK proteins and phosphorylation levels of MLC2v were severely reduced in the failing heart of trans-aortic constriction mice. Conclusions We identified a novel cardiac-MLCK which contributed mainly to cardiac MLC2v phosphorylation. Attenuation of cardiac-MLCK expression caused severe sarcomere disorganization both in vitro and in vivo implies its important roles in cardiac functions. Our results suggest that cardiac-MLCK mRNA expression may be upregulated to compensate for the lower expression and reduced phosphorylation of MLC2v in failing myocardium. As a possible therapeutic modality in patients with CHF, upregulation of cardiac-MLCK may promote sarcomere assembly and enhanced contractility of the failing heart


2019 ◽  
Vol 6 (2) ◽  
pp. 406-415 ◽  
Author(s):  
Akihiko Hodatsu ◽  
Noboru Fujino ◽  
Yuki Uyama ◽  
Osamu Tsukamoto ◽  
Atsuko Imai‐Okazaki ◽  
...  

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e66720 ◽  
Author(s):  
Audrey N. Chang ◽  
Jian Huang ◽  
Pavan K. Battiprolu ◽  
Joseph A. Hill ◽  
Kristine E. Kamm ◽  
...  

2008 ◽  
Vol 102 (5) ◽  
pp. 516-518 ◽  
Author(s):  
Yoshihiro Ishikawa ◽  
Reiko Kurotani

2015 ◽  
Vol 108 (2) ◽  
pp. 595a
Author(s):  
Audrey N. Chang ◽  
Pavan Battiprolu ◽  
Joseph A. Hill ◽  
Kristine E. Kamm ◽  
James T. Stull

2016 ◽  
Vol 7 ◽  
Author(s):  
Yasmin F. K. Islam ◽  
Ryan Joseph ◽  
Rajib R. Chowdhury ◽  
Robert H. Anderson ◽  
Hideko Kasahara

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