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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
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.
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:
- 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.