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Calcineurin and intracellular Ca2+-release channels: regulation or association?

G Bultynck1, E Vermassen, K Szlufcik

  • 1Department of Biological Sciences, Stanford University, Gilbert Hall, Room 208B, 371 Serra Mall, Stanford, CA 94305-5020, USA.

Biochemical and Biophysical Research Communications
|November 19, 2003
PubMed

Insights

Calcineurin, a phosphatase, regulates intracellular calcium channels like IP3R and RyR. This review clarifies its role in channel gating, gene expression, and potential drug side effects.

Area of Science:

  • Cellular Biology
  • Molecular Physiology
  • Biochemistry

Background:

  • Calcineurin (CaN) interacts with inositol 1,4,5-trisphosphate receptors (IP3Rs) and ryanodine receptors (RyRs), modulating their activity.
  • Conflicting data exists regarding CaN's molecular mechanisms and functional significance for these intracellular calcium channels.

Purpose of the Study:

  • To elucidate the functional importance of calcineurin in IP3R and RyR activity.
  • To explore mechanisms of Ca(2+)-dependent dephosphorylation affecting calcium channel gating.
  • To address the impact of calcineurin-inhibiting drugs and other associated enzymes on channel function.

Main Methods:

  • Literature review and critical analysis of existing studies.
  • Examination of calcineurin's role in regulating IP3R and RyR phosphorylation and gating.
  • Investigation of calcineurin's influence on gene expression related to calcium channels.

Main Results:

  • Calcineurin modulates IP3R and RyR phosphorylation, influencing their gating properties.
  • Immunosuppressive drugs used to inhibit calcineurin can have confounding side effects.
  • Other phosphatases and kinases associated with these channels may interfere with calcineurin's effects.

Conclusions:

  • Calcineurin plays a significant role in regulating intracellular calcium release channels.
  • Understanding calcineurin's complex interactions is crucial for interpreting experimental data and therapeutic interventions.
  • Calcineurin influences both channel activity and the expression of calcium-release channels, linking calcium signaling to gene expression.

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