Practice question

Ran is small 25 kilodalton Ras-family GTPase that specializes in marking nuclear versus cytoplasmic compartments, unlike Rab, Rho and Ras which control vesicle docking, actin remodeling and MAP kinase signaling elsewhere. Its nucleotide state differs across envelope because regulators are spatially segregated: RCC1 guanine nucleotide exchange factor bound to histones H2A-H2B inside nucleus generates high Ran-GTP, while RanGAP1 SUMOylated and anchored to RanBP2/Nup358 at cytoplasmic filaments together with RanBP1 accelerate GTP hydrolysis outside producing Ran-GDP. This partitioning creates steep gradient, nuclear Ran-GTP almost hundred-fold higher than cytoplasmic, providing chemical potential for transport. During import, importin heterodimer binds cargo where Ran-GTP low, traverses pore and meets Ran-GTP that dissociates complex. During export, high nuclear Ran-GTP promotes NES cargo association with exportins. Beyond transport, Ran-GTP gradient directs mitotic spindle assembly around chromosomes and nuclear envelope reformation after mitosis. Mutations locking Ran in GDP or GTP state inhibit both import and export and disrupt cell division, demonstrating dedicated role in compartment identity and cell cycle control beyond generic GTPase signaling.