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Biophys J, September 2002, p. 1421-1428, Vol. 83, No. 3

Regulation of Nuclear Pore Complex Conformation by IP3 Receptor Activation

David Moore-Nichols, Anne Arnott, and Robert C. Dunn

Department of Chemistry, University of Kansas, Lawrence, Kansas 66045 USA

In recent years, both the molecular architecture and functional dynamics of nuclear pore complexes (NPCs) have been revealed with increasing detail. These large, supramolecular assemblages of proteins form channels that span the nuclear envelope of cells, acting as crucial regulators of nuclear import and export. From the cytoplasmic face of the nuclear envelope, nuclear pore complexes exhibit an eightfold symmetric ring structure encompassing a central lumen. The lumen often appears occupied by an additional structure alternatively referred to as the central granule, nuclear transport complex, or nuclear plug. Previous studies have suggested that the central granule may play a role in mediating calcium-dependent regulation of diffusion across the nuclear envelope for intermediate sized molecules (10-40 kDa). Using atomic force microscopy to measure the surface topography of chemically fixed Xenopus laevis oocyte nuclear envelopes, we present measurements of the relative position of the central granule within the NPC lumen under a variety of conditions known to modify nuclear Ca2+ stores. These measurements reveal a large, ~9-nm displacement of the central granule toward the cytoplasmic face of the nuclear envelope under calcium depleting conditions. Additionally, activation of nuclear inositol triphosphate (IP3) receptors by the specific agonist, adenophostin A, results in a concentration-dependent displacement of central granule position with an EC50 of ~1.2 nM. The displacement of the central granule within the NPC is observed on both the cytoplasmic and nucleoplasmic faces of the nuclear envelope. The displacement is blocked upon treatment with xestospongin C, a specific inhibitor of IP3 receptor activation. These results extend previous models of NPC conformational dynamics linking central granule position to depletion of IP3 sensitive nuclear envelope calcium stores.

Biophys J, September 2002, p. 1421-1428, Vol. 83, No. 3
© 2002 by the Biophysical Society   0006-3495/02/09/1421/08  $2.00



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R. D. Jaggi, A. Franco-Obregon, and K. Ensslin
Quantitative Topographical Analysis of Nuclear Pore Complex Function Using Scanning Force Microscopy
Biophys. J., December 1, 2003; 85(6): 4093 - 4098.
[Abstract] [Full Text] [PDF]




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