Post-translational regulation of calsarcin-1 during pressure overload-induced cardiac hypertrophy

• Published in: Journal of molecular and cellular cardiology Vol. 48; no. 6; pp. 1206 - 1214
• Main Authors: Paulsson, Anna K., Franklin, Sarah, Mitchell-Jordan, Scherise A., Ren, Shuxun, Wang, Yibin, Vondriska, Thomas M.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2010
• Subjects: Amino Acid Sequence; Animals; Cardiac hypertrophy; Cardiomegaly - pathology; Cardiovascular; Carrier Proteins - biosynthesis; Carrier Proteins - physiology; Gene Expression Regulation; Hypertrophy; Male; Mice; Mice, Inbred BALB C; Microfilament Proteins; Molecular Sequence Data; Muscle Proteins - biosynthesis; Muscle Proteins - physiology; Myocardium - metabolism; Nucleus; Phosphorylation; Protein Processing, Post-Translational; Proteomics; Proteomics - methods; Sequence Homology, Amino Acid; Signal transduction; Cardiac hypertrophy; Signal transduction; Nucleus; Phosphorylation; Proteomics
• ISSN: 0022-2828; 1095-8584; 1095-8584
• DOI: 10.1016/j.yjmcc.2010.02.009

Chronic pressure overload to the heart leads to cardiac hypertrophy and failure through processes that involve reorganization of subcellular compartments and alteration of established signaling mechanisms. To identify proteins contributing to this process, we examined changes in nuclear-associated myofilament proteins as the murine heart undergoes progressive hypertrophy following pressure overload. Calsarcin-1, a negative regulator of calcineurin signaling in the heart, was found to be enriched in cardiac nuclei and displays increased abundance following pressure overload through a mechanism that is decoupled from transcriptional regulation. Using proteomics, we identified novel processing of this protein in the setting of cardiac injury and identified four residues subject to modification by phosphorylation. These studies are the first to determine mechanisms regulating calsarcin abundance during hypertrophy and failure and reveal the first evidence of post-translational modifications of calsarcin-1 in the myocardium. Overall, the findings expand the roles of calsarcins to include nuclear tasks during cardiac growth.