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Related Experiment Videos

Calcium, ATP and nuclear pore channel gating.

J O Bustamante1, E R Michelette, J P Geibel

  • 1The Nuclear Physiology Laboratory, Universidade Tiradentes, Aracaju, Sergipe, Brazil. omar@unitnet.com.br

Pflugers Archiv : European Journal of Physiology
|March 18, 2000
PubMed
Summary

Calcium and ATP regulate nuclear transport by silencing nuclear pore complex ion channels. This process, involving nuclear envelope calcium, synchronizes gene expression with cellular rhythms.

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biophysics

Background:

  • Nuclear envelope (NE) cisternal Ca2+ and cytosolic ATP are crucial for macromolecular transport (MMT) via nuclear pore complexes (NPCs).
  • Isolated cardiomyocyte nuclei exhibit intrinsic NPC ion channel (NPCC) behavior, modulated by MMT and blocked by mAb414.

Purpose of the Study:

  • To investigate the role of Ca2+ and ATP in regulating NPCC activity and MMT.
  • To elucidate the mechanism by which NE Ca2+ and ATP influence NPCC gating.

Main Methods:

  • Patch-clamp electrophysiology on isolated Dunning G prostate cancer cell nuclei.
  • Fluorescence microscopy using nuclear-targeted fluorochromes and FITC-labeled RNA.

Main Results:

Related Experiment Videos

  • Neither cytosolic Ca2+ nor ATP alone directly affects NPCC gating in isolated nuclei.
  • Simultaneous application of Ca2+ and ATP to the NE transiently silences NPCC activity by stimulating MMT.
  • NE Ca2+ loading/unloading cycles, after depletion by IP3 or chelators, did not affect subsequent channel gating, suggesting involvement of other factors.

    • Conclusions:

    • NE Ca2+ concentration ([Ca2+]NE) regulation by intracellular messengers synchronizes MMT and NPCC gating with cellular rhythms.
    • Ca2+ and IP3 waves can convert the NE into a Ca2+ barrier, impacting gene activity and expression.
    • This mechanism provides feedback on MMT and NPCC gating, linking cellular signaling to gene regulation.