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Monitoring ER/SR Calcium Release with the Targeted Ca2+ Sensor CatchER+
Published on: May 19, 2017
Calsequestrin accumulation in rough endoplasmic reticulum promotes perinuclear Ca2+ release
Ang Guo1, Steven E Cala, Long-Sheng Song
1Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, Iowa 52242, USA.
The Journal of Biological Chemistry
|March 30, 2012
Summary
Cardiac calsequestrin (CSQ2) in the perinuclear endoplasmic reticulum (ER) enhances nuclear calcium (Ca2+) signaling and promotes Ca2+ waves. This ER-localized CSQ2 can independently influence Ca2+ signaling in cardiomyocytes.
Area of Science:
- Cardiology
- Cell Biology
- Molecular Physiology
Background:
- The regulation of calcium (Ca2+) by perinuclear endoplasmic/sarcoplasmic reticulum (ER/SR) cisternae in cardiomyocytes is not fully understood.
- Cardiac calsequestrin (CSQ2) plays a crucial role in intracellular Ca2+ handling, but its specific role in perinuclear Ca2+ signaling requires further investigation.
Purpose of the Study:
- To investigate how manipulating the subcellular distribution of CSQ2 affects perinuclear Ca2+ signaling in cardiomyocytes.
- To determine the mechanisms by which perinuclear-enriched CSQ2 influences nuclear and cytosolic Ca2+ transients and Ca2+ waves.
Main Methods:
- Overexpression of CSQ2-DsRed, which accumulates in the perinuclear rough ER, in adult ventricular myocytes using adenoviral vectors.
- Comparison of Ca2+ transients, Ca2+ wave propagation, and cellular hypertrophy induced by perinuclear-enriched CSQ2-DsRed versus normally distributed CSQ2-WT.
- Assessment of the involvement of SR/ER Ca2+-ATPase, ryanodine receptor type 2, and inositol 1,4,5-trisphosphate receptor type 2 in CSQ2-mediated Ca2+ signaling.
Main Results:
- Perinuclear-enriched CSQ2-DsRed significantly enhanced nuclear Ca2+ transients more than cytosolic Ca2+ transients, unlike normally distributed CSQ2-WT.
- Overexpression of CSQ2-DsRed led to more actively propagating Ca2+ waves originating from perinuclear regions compared to CSQ2-WT.
- CSQ2-DsRed was more potent in inducing cellular hypertrophy in neonatal cardiomyocytes than CSQ2-WT, and SR/ER Ca2+-ATPase and ryanodine receptor type 2 activities were essential for perinuclear Ca2+ waves.
Conclusions:
- CSQ2 retention in the rough ER/perinuclear region promotes perinuclear Ca2+ signaling and ryanodine receptor type 2-mediated Ca2+ waves.
- Rough ER-localized Ca2+ stores can independently regulate cytosolic/nucleoplasmic Ca2+ levels, impacting Ca2+ dependent signaling.
- These findings offer new insights into CSQ2's role in Ca2+ homeostasis and suggest potential mechanisms in cardiac health and disease.
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