Nucleo-Cytoplasmic Exchange

ID #2259

what happens in the nucleus that makes the importin let go of protein? Is that simply the GTP INSIDE the nucleus? I read that GTP releases importin so it can bind to a new cargo protein in the cytoplasm. Then the GDP in the cytoplasm gets transported back to the nucleus.

If you look at one of slides from lecture 25 illustrating protein import into the nucleus, you'll see an importin bound to its protein cargo's NLS signal. Once they are in the nucleus, importin has done its job and now we need to get the importin to let go of its NLS-containing cargo. At this point, a Ran-GTP binds to the importin. This binding event causes a change in conformation of the importin protein that makes it let go of its cargo in the nucleus. The importin-Ran-GTP complex is then exported out of the nucleus through the nuclear pore complex into the cytoplasm. The GTPase-activating protein (GAP) in the cytoplasm (not shown in the figure) hydrolyzes the GTP on Ran to GDP, and this leads to the release of the importin. Now importin goes back to its original conformation, allowing it to bind to the next cargo/protein that presents an NLS and start the process all over again. Separately, Ran-GDP is able to get back into the nucleus and using the exchange system provided by GEF, can become Ran-GTP again to be ready for the next round of nuclear export of the importin itself. 

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