Regulatory Light Chain Phosphorylation Mimic S15D Causes Partial Rescue of Isometric Force Production in FHC Causing Mutation D166V
نویسندگان
چکیده
منابع مشابه
Constitutive phosphorylation of cardiac myosin regulatory light chain prevents development of hypertrophic cardiomyopathy in mice.
Myosin light chain kinase (MLCK)-dependent phosphorylation of the regulatory light chain (RLC) of cardiac myosin is known to play a beneficial role in heart disease, but the idea of a phosphorylation-mediated reversal of a hypertrophic cardiomyopathy (HCM) phenotype is novel. Our previous studies on transgenic (Tg) HCM-RLC mice revealed that the D166V (Aspartate166 → Valine) mutation-induced ch...
متن کاملMyosin regulatory light chain mutation found in hypertrophic cardiomyopathy patients increases isometric force production in transgenic mice.
FHC (familial hypertrophic cardiomyopathy) is a heritable form of cardiac hypertrophy caused by mutations in genes encoding sarcomeric proteins. The present study focuses on the A13T mutation in the human ventricular myosin RLC (regulatory light chain) that is associated with a rare FHC variant defined by mid-ventricular obstruction and septal hypertrophy. We generated heart-specific Tg (transg...
متن کاملMyosin light chain phosphorylation to the rescue.
A common cause of heart failure is hypertrophic cardiomyopathy (HCM) with a prevalence of at least 1 in 500 in adults (1); more recent data suggest that the prevalence of HCM may be as high as 1 in 200 (2). HCM is characterized by disorganized myocyte structure; formation of excess connective tissue (fibrosis); and, importantly, enlargement of cardiac myocytes that increases the ventricular wal...
متن کاملThe effect of myosin RLC phosphorylation in normal and cardiomyopathic mouse hearts
Phosphorylation of the myosin regulatory light chain (RLC) by Ca(2+)-calmodulin-activated myosin light chain kinase (MLCK) is known to be essential for the inotropic function of the heart. In this study, we have examined the effects of MLCK-phosphorylation of transgenic (Tg) mouse cardiac muscle preparations expressing the D166V (aspartic acid to valine)-RLC mutation, identified to cause famili...
متن کاملRevisiting Frank–Starling: regulatory light chain phosphorylation alters the rate of force redevelopment (k tr) in a length‐dependent fashion
KEY POINTS Regulatory light chain (RLC) phosphorylation has been shown to alter the ability of muscle to produce force and power during shortening and to alter the rate of force redevelopment (ktr ) at submaximal [Ca(2+) ]. Increasing RLC phosphorylation ∼50% from the in vivo level in maximally [Ca(2+) ]-activated cardiac trabecula accelerates ktr . Decreasing RLC phosphorylation to ∼70% of the...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Biophysical Journal
سال: 2012
ISSN: 0006-3495
DOI: 10.1016/j.bpj.2011.11.3035