PUBLICATION

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

Authors
Seguchi, O., Takashima, S., Yamazaki, S., Asakura, M., Asano, Y., Shintani, Y., Wakeno, M., Minamino, T., Kondo, H., Furukawa, H., Nakamaru, K., Naito, A., Takahashi, T., Ohtsuka, T., Kawakami, K., Isomura, T., Kitamura, S., Tomoike, H., Mochizuki, N., and Kitakaze, M.
ID
ZDB-PUB-070924-8
Date
2007
Source
J. Clin. Invest.   117(10): 2812-2824 (Journal)
Registered Authors
Kawakami, Koichi
Keywords
none
MeSH Terms
  • Adult
  • Aged
  • Amino Acid Sequence
  • Animals
  • Cardiac Myosins/metabolism
  • Cardiac Output, Low/enzymology*
  • Cardiac Output, Low/genetics
  • Cardiac Output, Low/pathology
  • Cells, Cultured
  • Cloning, Molecular
  • Embryo, Nonmammalian/metabolism
  • Female
  • Heart/embryology*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Myocardium/enzymology
  • Myocardium/ultrastructure*
  • Myocytes, Cardiac/metabolism
  • Myocytes, Cardiac/ultrastructure
  • Myosin Light Chains/metabolism
  • Myosin-Light-Chain Kinase/antagonists & inhibitors
  • Myosin-Light-Chain Kinase/genetics
  • Myosin-Light-Chain Kinase/metabolism*
  • Myosin-Light-Chain Kinase/physiology*
  • Oligonucleotide Array Sequence Analysis
  • Oligoribonucleotides, Antisense/pharmacology
  • Organogenesis*/genetics
  • Rats
  • Sarcomeres/metabolism*
  • Up-Regulation
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/physiology*
PubMed
17885681 Full text @ J. Clin. Invest.
Abstract
Marked sarcomere disorganization is a well-documented characteristic of cardiomyocytes in the failing human myocardium. Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC2v), which is involved in the development of human cardiomyopathy, is an important structural protein that affects physiologic cardiac sarcomere formation and heart development. Integrated cDNA expression analysis of failing human myocardia uncovered a novel protein kinase, cardiac-specific myosin light chain kinase (cardiac-MLCK), which acts on MLC2v. Expression levels of cardiac-MLCK were well correlated with the pulmonary arterial pressure of patients with heart failure. In cultured cardiomyocytes, knockdown of cardiac-MLCK by specific siRNAs decreased MLC2v phosphorylation and impaired epinephrine-induced activation of sarcomere reassembly. To further clarify the physiologic roles of cardiac-MLCK in vivo, we cloned the zebrafish ortholog z-cardiac-MLCK. Knockdown of z-cardiac-MLCK expression using morpholino antisense oligonucleotides resulted in dilated cardiac ventricles and immature sarcomere structures. These results suggest a significant role for cardiac-MLCK in cardiogenesis.
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