Final answer:
GTP-Ran regulates the directionality of import by importin proteins through differential interactions within the nucleus and cytoplasm, causing disassembly of importin-cargo complexes in the nucleus, and allowing importin recycling following GTP hydrolysis.
Step-by-step explanation:
The control of the directionality of import by importin proteins is a vital aspect of nuclear transport, which is critical for the correct functioning of eukaryotic cells. In this process, the GTP-bound form of a small GTPase protein called Ran (GTP-Ran) plays a crucial role. GTP-Ran provides directionality to the transport process by differentially interacting with importin proteins inside and outside of the nucleus. Nuclear import is executed by the binding of importin to the nuclear localization signal (NLS) on a cargo protein in the cytoplasm, forming a complex that is then transported through the nuclear pore complex.
Once inside the nucleus, high concentrations of GTP-Ran cause dissociation of the importin-cargo complex by binding to importin, which releases the cargo protein. The importin-RanGTP complex then translocates back to the cytoplasm, where Ran's intrinsic GTPase activity, or other regulatory proteins, stimulates the hydrolysis of GTP to GDP. This hydrolysis causes a conformational change in Ran, leading to the dissociation of RanGDP from importin, and allowing importin to participate in another round of nuclear import.
In the context of cancer, as noted in the reference material, the inhibition of GTPase activity of another GTPase, the RAS G-protein, can prevent the normal hydrolysis of GTP to GDP, leading to uncontrolled signaling and cell growth, contributing to the development of cancer. While the specific details differ between Ran and RAS G-proteins, the principle that GTP-binding and hydrolysis regulate the function of these proteins is a key concept in understanding their role in cellular processes.
GTP-Ran regulates importin directionality by causing importin-cargo complex disassembly in the nucleus and allowing for importin's return to the cytoplasm. Ran's GTPase activity is essential for recycling importin, underscoring its role in the controlled import of proteins into the nucleus.