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• W2114549166 abstract "Rationale: The ability of a cell to independently regulate nuclear and cytosolic Ca 2+ signaling is currently attributed to the differential distribution of inositol 1,4,5-trisphosphate receptor channel isoforms in the nucleoplasmic versus the endoplasmic reticulum. In cardiac myocytes, T-tubules confer the necessary compartmentation of Ca 2+ signals, which allows sarcomere contraction in response to plasma membrane depolarization, but whether there is a similar structure tunneling extracellular stimulation to control nuclear Ca 2+ signals locally has not been explored. Objective: To study the role of perinuclear sarcolemma in selective nuclear Ca 2+ signaling. Methods and Results: We report here that insulin-like growth factor 1 triggers a fast and independent nuclear Ca 2+ signal in neonatal rat cardiac myocytes, human embryonic cardiac myocytes, and adult rat cardiac myocytes. This fast and localized response is achieved by activation of insulin-like growth factor 1 receptor signaling complexes present in perinuclear invaginations of the plasma membrane. The perinuclear insulin-like growth factor 1 receptor pool connects extracellular stimulation to local activation of nuclear Ca 2+ signaling and transcriptional upregulation through the perinuclear hydrolysis of phosphatidylinositol 4,5-biphosphate inositol 1,4,5-trisphosphate production, nuclear Ca 2+ release, and activation of the transcription factor myocyte-enhancing factor 2C. Genetically engineered Ca 2+ buffers—parvalbumin—with cytosolic or nuclear localization demonstrated that the nuclear Ca 2+ handling system is physically and functionally segregated from the cytosolic Ca 2+ signaling machinery. Conclusions: These data reveal the existence of an inositol 1,4,5-trisphosphate–dependent nuclear Ca 2+ toolkit located in direct apposition to the cell surface, which allows the local control of rapid and independent activation of nuclear Ca 2+ signaling in response to an extracellular ligand." @default.
• W2114549166 created "2016-06-24" @default.
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• W2114549166 date "2013-01-18" @default.
• W2114549166 modified "2023-10-01" @default.
• W2114549166 title "Local Control of Nuclear Calcium Signaling in Cardiac Myocytes by Perinuclear Microdomains of Sarcolemmal Insulin-Like Growth Factor 1 Receptors" @default.
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• W2114549166 doi "https://doi.org/10.1161/circresaha.112.273839" @default.
• W2114549166 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23118311" @default.
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