PerspectiveSignaling to the Nucleus

The Regulation of Nuclear Membrane Permeability by Ca2+ Signaling: A Tightly Regulated Pore or a Floodgate?

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Science's STKE  15 May 2007:
Vol. 2007, Issue 386, pp. pe24
DOI: 10.1126/stke.3862007pe24

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The nuclear pore complex functions both to separate and to connect the nucleus and the cytoplasm. Minute-to-minute changes in gene expression depend on rapid translocation of transcription factors and other regulatory proteins from the cytosol into the nucleus. However, a controversy exists as to whether cell signaling allows large molecules to enter the nucleus through tightly regulated facilitated transport or by the opening of a floodgate. A recent report suggesting that some hormones increase nuclear permeability through changes in intracellular Ca2+ concentration has reignited this debate. Here, I consider both the basic permeability of the nuclear membrane under resting conditions and the effects of Ca2+ on the permeability of the nuclear pore. I discuss facilitated transport through the nuclear pore complex, with particular attention to the nuclear transport of Ca2+-CaM signaling complexes. Finally, I weigh the arguments in favor of a generic increase in permeability versus stimulation of facilitated transport as possible mechanisms for mediating cell signaling to the nucleus.

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