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Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms
13:40

Live Cell Calcium Imaging Combined with siRNA Mediated Gene Silencing Identifies Ca2+ Leak Channels in the ER Membrane and their Regulatory Mechanisms

Published on: July 7, 2011

Calcium controls gene expression via three distinct pathways that can function independently of the

C M Johnson1, C S Hill, S Chawla

  • 1Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 2QH, England.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|August 15, 1997
PubMed

Insights

Calcium ions regulate gene expression through three distinct pathways, impacting neuronal gene transcription differently across cell types. These calcium-signaling mechanisms control the c-fos gene promoter activity.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Signaling

Background:

  • Calcium ions are crucial second messengers in neuronal electrical activity, regulating gene expression.
  • The intricate calcium-signaling pathways and cellular machinery governing transcriptional activation remain incompletely understood.

Purpose of the Study:

  • To elucidate the complexity of calcium-signaling pathways controlling gene expression.
  • To investigate the cell type-specific mechanisms of calcium-mediated transcriptional activation using the c-fos gene as a model.

Main Methods:

  • Utilized the c-fos gene promoter to study calcium-regulated transcription.
  • Investigated the roles of the serum response element (SRE), ternary complex factor (TCF), serum response factor (SRF), and cyclic AMP response element (CRE).
  • Examined the involvement of Ras/MAP kinases (ERKs) signaling pathways, including RasN17 and PD 98059.

Main Results:

  • Identified three independent calcium-signaling mechanisms controlling the c-fos promoter, with cell type-dependent functional significance.
  • The SRE integrates two calcium pathways: one TCF-dependent (PC12 cells) and another TCF-independent (AtT20 cells, hippocampal neurons).
  • A third calcium-regulated pathway targets the CRE, operating independently of Ras/MAP kinases (ERKs).

Conclusions:

  • Calcium can stimulate gene expression through distinct TCF-, SRF-, and CRE-linked pathways.
  • These pathways can operate independently of the Ras/MAP kinases (ERKs) signaling cascade.
  • The functional significance of these calcium-signaling mechanisms is cell type-dependent.

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