Mechanisms controlling gene expression by nuclear calcium signals
G E Hardingham1, F H Cruzalegui, S Chawla
1MRC Laboratory of Molecular Biology, Cambridge, UK.
Cell Calcium
|May 28, 1998
Summary
Nuclear calcium transients regulate gene expression in neurons. This process, distinct from cytoplasmic signals, involves the cAMP response element (CRE) and CREB, potentially mediated by nuclear calcium/calmodulin-dependent protein kinase IV.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Nuclear calcium acts as a key regulator of gene expression in electrically excitable cells after membrane depolarization.
- Cytoplasmic calcium signals are known regulators of gene expression, but the role of nuclear calcium has been less understood.
Purpose of the Study:
- To investigate nuclear calcium transients in hippocampal neurons.
- To elucidate the mechanisms by which nuclear calcium influences gene transcription.
- To identify potential mediators of nuclear calcium-induced gene regulation.
Main Methods:
- Studied nuclear calcium transients in hippocampal neurons.
- Activated calcium influx via L-type voltage-sensitive calcium channels and NMDA receptors.
- Induced calcium release from intracellular caffeine-sensitive stores.
- Investigated the involvement of the cAMP response element (CRE) and CRE binding protein (CREB).
- Examined the expression and potential role of nuclear calcium/calmodulin dependent protein kinase IV.
Main Results:
- Observed nuclear calcium transients in hippocampal neurons under various stimulation conditions.
- Demonstrated that increased nuclear calcium activates gene transcription through a mechanism distinct from cytoplasmic calcium signaling.
- Identified the involvement of the cAMP response element (CRE) and CRE binding protein (CREB) in this nuclear calcium-mediated transcriptional regulation.
- Confirmed the expression of nuclear calcium/calmodulin dependent protein kinase IV in cultured hippocampal neurons and AtT20 cells.
Conclusions:
- Nuclear calcium transients are significant regulators of gene expression in hippocampal neurons.
- The mechanism of nuclear calcium-induced transcription involves CRE and CREB, differing from cytoplasmic calcium pathways.
- Nuclear calcium/calmodulin dependent protein kinase IV is a potential mediator of nuclear calcium's effect on gene transcription.
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