Nucleo-Cytoplasmic Exchange

ID #2260

Could you please explain this: High concentration of Ran-GTP in the nucleus determines the directionality of nuclear transport of cargo proteins. Does that mean if there is high concentration of RAN-GTP in the cytoplasm, that there would be more exporting than importing?

Before we answer the question, a few key points to remember: We know that there is a concentration difference of Ran-GTP, where it is very plentiful in the nucleus and Ran-GDP is plentiful in the cytoplasm, and we know that the GAP protein in the cytplasm has the ability to hydrolyze the GTP piggy-backed on Ran to GDP, while the GEF protein in the nucleus has the ability to exchange GDP for a new GTP in Ran (leading to the production of more Ran-GTP in the nucleus, thus causing the gradient difference). The high concentration of Ran-GTP in the nucleus has two effects on the directionality of the nuclear transport of proteins: (1) it promotes the release of the NLS-containing protein cargo from the importin once they are in the nucleus; and (2) Ran-GTP promotes the binding of NES-containing protein cargo to exportin, and altogether, the complex gets exported out of the nucleus into the cytoplasm.
To answer your question, the gradient can't go the other way because there is no GEF in the cytoplasm. The only way you could reverse the whole system is by also reversing the position of Ran GAP and Ran GEF, but you'd still run into the problem that NLS cargo bound by importin goes into the nucleus and NES cargo bound by exportin goes out of the nucleus, so you'd also have to reverse the directionality of the nuclear pore, which is a pretty complex mental exercise!

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