title: STIM1-dependent Ca(2+) microdomains are required for myofilament remodeling and signaling in the heart.
abstract: In non-excitable cells stromal interaction molecule 1 (STIM1) is a key element in the generation of Ca(2+) signals that lead to gene expression, migration and cell proliferation. A growing body of literature suggests that STIM1 plays a key role in the development of pathological cardiac hypertrophy. However, the precise mechanisms involving STIM-dependent Ca(2+) signaling in the heart are not clearly established. Here, we have investigated the STIM1-associated Ca(2+) signals in cardiomyocytes and their relevance to pathological cardiac remodeling. We show that mice with inducible, cardiac-restricted, ablation of STIM1 exhibited left ventricular reduced contractility, which was corroborated by impaired single cell contractility. The spatial properties of STIM1-dependent Ca(2+) signals determine restricted Ca(2+) microdomains that regulate myofilament remodeling and activate spatially segregated pro-hypertrophic factors. Indeed, mice lacking STIM1 showed less adverse structural remodeling in response to pressure overload-induced cardiac hypertrophy. These results highlight how STIM1-dependent Ca(2+) microdomains have a major impact on intracellular Ca(2+) homeostasis, cytoskeletal remodeling and cellular signaling, even when excitation-contraction coupling is present.
authors.affiliation: Department of Physiology Medicine, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA.
authors.forename: Cory
authors.initials: C
authors.lastname: Parks
authors.affiliation: Department of Physiology Medicine, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA.
authors.forename: Mohammad Afaque
authors.initials: MA
authors.lastname: Alam
authors.affiliation: Department of Comparative Medicine, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Sullivan
authors.affiliation: Department of Physiology Medicine, University of Tennessee Health Sciences Center, Memphis, TN 38163, USA.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Mancarella
mesh_terms: D000818:Animals; D020013:Calcium Signaling; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D006321:Heart / Q000502:physiology*; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000502:physiology*; D009210:Myofibrils / Q000378:metabolism*; D051381:Rats; D000071737:Stromal Interaction Molecule 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1