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Related Experiment Videos

Source of nuclear calcium signals

N L Allbritton1, E Oancea, M A Kuhn

  • 1Department of Neurobiology, Stanford University, CA 94305.

Proceedings of the National Academy of Sciences of the United States of America
|December 20, 1994
PubMed
Summary

Nuclear calcium (Ca2+) signals are not independently controlled. Instead, nuclear Ca2+ increases follow cytosolic Ca2+ increases with a slight delay, likely due to diffusion through nuclear pores.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Nuclear calcium (Ca2+) transients regulate gene expression and nuclear functions.
  • The precise control mechanisms and origins of nuclear Ca2+ signals remain incompletely understood.
  • Investigating the relationship between cytosolic and nuclear Ca2+ dynamics is crucial for understanding cellular signaling.

Purpose of the Study:

  • To determine if nuclear Ca2+ signals are regulated independently of the cytoplasm.
  • To elucidate the temporal relationship between cytosolic and nuclear Ca2+ increases.
  • To investigate the role of cytosolic Ca2+ stores in nuclear Ca2+ signaling.

Main Methods:

  • Synthesis of a nucleus-targeted fluorescent Ca2+ indicator by conjugating a nuclear localization peptide to Calcium Green dextran.
  • Stimulation of rat basophilic leukemia cells using antigen or photolytic uncaging of inositol 1,4,5-trisphosphate.
  • Development and application of heparin-dextran, a nuclear-excluded inhibitor of the inositol 1,4,5-trisphosphate receptor, to block cytosolic Ca2+ release.

Main Results:

  • Antigen or inositol 1,4,5-trisphosphate stimulation induced transient increases in both nuclear and cytosolic Ca2+ concentrations.
  • Nuclear Ca2+ elevations followed cytosolic Ca2+ increases within 200 ms.
  • Inhibition of cytosolic Ca2+ release using heparin-dextran suppressed Ca2+ transients in both the nucleus and cytosol.

Conclusions:

  • Nuclear Ca2+ levels are not independently controlled but are directly influenced by cytosolic Ca2+ dynamics.
  • Nuclear Ca2+ increases are a consequence of cytosolic Ca2+ elevations, with a short delay attributed to diffusion through nuclear pores.
  • Cytosolic Ca2+ release is essential for generating nuclear Ca2+ signals.

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