Post-translational regulation of calsarcin-1 during pressure overload-induced cardiac hypertrophy.
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.
Paulsson
Anna K
AK
Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Franklin
Sarah
S
Mitchell-Jordan
Scherise A
SA
Ren
Shuxun
S
Wang
Yibin
Y
Vondriska
Thomas M
TM
D000595:Amino Acid Sequence; D000818:Animals; D006332:Cardiomegaly / Q000473:pathology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000502:physiology; D005786:Gene Expression Regulation; D006984:Hypertrophy; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods; D017386:Sequence Homology, Amino Acid
D002352:Carrier Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; C523646:Myoz2 protein, mouse