Nucleo-Cytoplasmic Exchange

ID #1217

I am having some trouble understanding exactly what makes an importin release the cargo protein once inside the nucleus. I know that the energy from GTP hydrolysis in the cytoplasm is is used for recycling that importin so that it will start another round of importing proteins or other things. But once the importin is inside the nucleus, what makes it let go of the NLS of the protein? Do they just no longer recognize the NLS once inside the nucleus? Or is it just their job to disassemble once inside the nucleus? I'm not sure I understand why the importin just lets go of the cargo protein.

This is an excellent question. Based solely on what we've learned this semester, in general about cells and specifically about importins and exportins, there doesn't appear to be a logical reason for an importin to "let go" of an NLS once it's inside the nucleus. And to be honest, when something like that comes up in MCB 150, it's most likely because I'm not telling you the whole story. That's certainly the case here, and I applaud your line of reasoning and questioning "why."

What I'm about to write will NOT be on the exam, but I'm always happy to answer the questions if they come up. As I've mentioned casually in either office hours, or perhaps elsewhere in this forum, there's more to the complex of material that's entering or exiting the nucleus than just the cargo and the importin or exportin. There's also another molecule involved called Ran. Ran actually has a molecule of GTP associated with it. So out in the cytoplasm, you have an importin+Ran+GTP. And remember, GTP hydrolysis happens out in the cytoplasm. So this changes the conformation of importin+Ran+GDP in such a way that it can bind a NLS and take the cargo protein into the nucleus. Once in the nucleus, there is an enzyme which swaps out the GDP for a fresh GTP in Ran. This changes the conformation of the importin back to a state where it CANNOT bind a NLS, so it lets go! Then the importin+Ran+GTP heads back out to the cytoplasm, where the GTP gets hydrolyzed, and the cycle can continue.

Now aren't you glad that's not part of what's going to be on the exam?! :)

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