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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., ((c) 2010 Elsevier Ltd. All rights reserved.)

Macrophage stimulating protein (MSP) is a pleiotropic growth factor that signals via the RON receptor tyrosine kinase. Here we demonstrate that MSP increases the proportion of cultured adult mouse DRG neurons displaying discernable neuritic processes and promotes the elongation and branching of these processes in a dose dependent manner. RON expression in adult DRG is largely restricted to nerve growth factor (NGF)-responsive nociceptive neurons, and MSP mimics the effects of NGF by increasing the expression of several mRNAs that encode functionally important proteins that are characteristically expressed by this neuronal sub-population. MSP mRNA is expressed at high levels in the peripheral target fields of DRG somatic afferents, but is undetectable in DRG, spinal cord or freshly dissected sciatic nerve. These results suggest that MSP is a peripheral target-derived neurotrophic factor for NGF-responsive adult DRG neurons.