Journal article
Calsequestrin Accumulation in Rough Endoplasmic Reticulum Promotes Perinuclear Ca2+ Release
The Journal of biological chemistry, Vol.287(20), pp.16670-16680
05/11/2012
DOI: 10.1074/jbc.M112.340927
PMCID: PMC3351355
PMID: 22457350
Abstract
Molecular mechanisms underlying Ca2+ regulation by perinuclear endoplasmic/sarcoplasmic reticulum (ER/SR) cisternae in cardiomyocytes remain obscure. To investigate the mechanisms of changes in cardiac calsequestrin ( CSQ2) trafficking on perinuclear Ca2+ signaling, we manipulated the subcellular distribution of CSQ2 by overexpression of CSQ2-DsRed, which specifically accumulates in the perinuclear rough ER. Adult ventricular myocytes were infected with adenoviruses expressing CSQ2-DsRed, CSQ2-WT, or empty vector. We found that perinuclear enriched CSQ2-DsRed, but not normally distributed CSQ2-WT, enhanced nuclear Ca2+ transients more potently than cytosolic Ca2+ transients. Overexpression of CSQ2-DsRed produced more actively propagating Ca2+ waves from perinuclear regions than did CSQ2-WT. Activities of the SR/ER Ca2+-ATPase and ryanodine receptor type 2, but not inositol 1,4,5-trisphosphate receptor type 2, were required for the generation of these perinuclear initiated Ca2+ waves. In addition, CSQ2-DsRed was more potent than CSQ2-WT in inducing cellular hypertrophy in cultured neonatal cardiomyocytes. Our data demonstrate for the first time that CSQ2 retention in the rough ER/perinuclear region promotes perinuclear Ca2+ signaling and predisposes to ryanodine receptor type 2-mediated Ca2+ waves from CSQ2-enriched perinuclear compartments and myocyte hypotrophy. These findings provide new insights into the mechanism of CSQ2 in Ca2+ homeostasis, suggesting that rough ER-localized Ca2+ stores can operate independently in raising levels of cytosolic/nucleoplasmic Ca2+ as a source of Ca2+ for Ca2+-dependent signaling in health and disease.
Details
- Title: Subtitle
- Calsequestrin Accumulation in Rough Endoplasmic Reticulum Promotes Perinuclear Ca2+ Release
- Creators
- Ang Guo - Roy J. and Lucille A. Carver College of MedicineSteven E. Cala - Wayne State UniversityLong-Sheng Song - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.287(20), pp.16670-16680
- DOI
- 10.1074/jbc.M112.340927
- PMID
- 22457350
- PMCID
- PMC3351355
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Amer Soc Biochemistry Molecular Biology Inc
- Number of pages
- 11
- Grant note
- R01 HL090905; R01 HL062586 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01HL090905 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) 0635056N / American Heart Association
- Language
- English
- Date published
- 05/11/2012
- Academic Unit
- Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Internal Medicine
- Record Identifier
- 9984288723002771
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