title: Overexpression of myosin phosphatase reduces Ca(2+) sensitivity of contraction and impairs cardiac function.
abstract: BACKGROUND
  Phosphorylation of the regulatory light chain of myosin (MLC) has roles in cardiac function. In vitro, myosin phosphatase target subunit 2 (MYPT2) is a strongly suspected regulatory subunit of cardiac myosin phosphatase (MP), but there is no in-vivo evidence regarding the functions of MYPT2 in the heart.
  
  
  RESULTS
  Transgenic mice (Tg) overexpressing MYPT2 were generated using the alpha-MHC promoter. Tg hearts showed an increased expression of MYPT2 and concomitant increase of the endogenous catalytic subunit of type 1 phosphatase (PP1cdelta), resulting in an increase of the MP holoenzyme. The level of phosphorylation of ventricular MLC was reduced. The pCa-tension relationship, using beta-escin permeabilized fibers, revealed decreased Ca(2+) sensitization of contraction in the Tg heart. LV enlargement with associated impairment of function was observed in the Tg heart and ultrastructural examination showed cardiomyocyte degeneration.
  
  
  CONCLUSIONS
  Overexpression of MYPT2 and the increase in PP1cdelta resulted in an increase of the MP holoenzyme and a decrease in the level of MLC phosphorylation. The latter induced Ca(2+) desensitization of contraction and decreased LV contractility, resulting in LV enlargement. Thus, MYPT2 is truly the regulatory subunit of cardiac MP in-vivo and plays a significant role in modulating cardiac function. (Circ J 2010; 74: 120 - 128).
authors: Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Japan.
authors: Hideo
authors: H
authors: Mizutani
authors: Ryuji
authors: R
authors: Okamoto
authors: Nobuyuki
authors: N
authors: Moriki
authors: Katsuhisa
authors: K
authors: Konishi
authors: Masaya
authors: M
authors: Taniguchi
authors: Satoshi
authors: S
authors: Fujita
authors: Kaoru
authors: K
authors: Dohi
authors: Katsuya
authors: K
authors: Onishi
authors: Noboru
authors: N
authors: Suzuki
authors: Shinji
authors: S
authors: Satoh
authors: Naoki
authors: N
authors: Makino
authors: Takeo
authors: T
authors: Itoh
authors: David J
authors: DJ
authors: Hartshorne
authors: Masaaki
authors: M
authors: Ito
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006321:Heart / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D018994:Myosin Light Chains / Q000378:metabolism; D043263:Myosin-Light-Chain Phosphatase / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism
chemical_list: D018994:Myosin Light Chains; D021122:Protein Subunits; D043263:Myosin-Light-Chain Phosphatase; D002118:Calcium