Abstract 17732: Identification of Stromal Interaction Molecule 1 Complexes in Cardiac Hypertrophy
Abnormalities in intracellular calcium signaling initiate and promote sustained pathological cardiac hypertrophy. Stromal interaction molecule 1 (STIM1) is an essential calcium sensor that activates calcium influx in response to calcium depletion in the endoplasmic reticulum (ER) in many cells. Previously, we found that STIM1 is activated and functional in hypertrophic cardiomyocytes where it controls store-dependent and -independent calcium influxes that further promote the development of cardiac hypertrophy. To understand the regulatory mechanisms of STIM1 during hypertrophic remodeling, we performed interactome analyses on a rat model of compensated cardiac hypertrophy resulting from pressure overload by thoracic aortic banding. STIM1 complexes were immunoprecipitated from cardiomyocytes isolated from either control or aortic-banded hearts. Electrospray ionization tandem mass spectrometry analysis identified a total of 93 proteins that were reliably enriched in the STIM1 immunoprecipitates in multiple independent experiments. Silver staining of the isolated complexes revealed distinct patterns of associated proteins in the disease states. STIM1 complexes were enriched in hypertrophic hearts with a total of 78 identified proteins as compared to 53 proteins in control hearts. Only 38 proteins were associated with STIM1 in both control and diseased conditions. Next, we performed a functional classification of our interactome data. Gene Ontology (GO) analysis showed distinct functional GO categories including ion channels, cellular signaling molecules, apoptosis, ER function and mitochondrial function. We finally mapped the identified proteins using the STRING interaction database that further revealed functional relationships between the STIM1 complex proteins and significant changes during hypertrophic remodeling. These findings identify multiple specific functional complexes for STIM1 that are recruited during cardiac hypertrophy. These data support a model where STIM1 is a dynamic signal transducer that can interact with a diversity of proteins depending on the pathophysiological conditions.
Author Disclosures: A. Lee: None. C. Kho: None. L. Bénard: None. A. Chaanine: None. R. Hajjar: None. J. Hulot: None.
- © 2014 by American Heart Association, Inc.