RanGTPRanGDP

RanGTPRanGDP refers to the two nucleotide-bound forms of Ran, a small GTPase of the Ras superfamily, and to the cellular cycle that interconverts them. In the cell, Ran cycles between GTP- and GDP-bound states, with the two forms concentrated in different compartments to create a functional gradient that directs nucleocytoplasmic transport and other Ran-dependent processes.

The Ran gradient is established by RCC1, a guanine nucleotide exchange factor bound to chromatin in the nucleus, which converts Ran-GDP to Ran-GTP. In the cytoplasm, RanGAP1 stimulates GTP hydrolysis to Ran-GDP, aided by RanBP1 and the nucleoporin RanBP2 at the NPC. As a result, RanGTP predominates in the nucleus and RanGDP in the cytoplasm.

In nuclear transport, importins and exportins rely on this gradient. Cargo proteins bearing import signals bind importins in the cytoplasm; upon entry into the nucleus, RanGTP binds importins causing cargo release. For export, cargo with export signals forms a complex with RanGTP and exportin in the nucleus; once in the cytoplasm, GTP hydrolysis releases cargo.

RanGTP also regulates mitosis and nuclear envelope reassembly. A chromosome-proximal RanGTP gradient releases spindle assembly factors from inhibitory complexes, promoting microtubule nucleation and spindle formation. After chromosome segregation, RanGTP contributes to reassembling the nuclear envelope around daughter chromatin.

Variants and terminology: RanGTP and RanGDP are functional states used in studies; mutants such as RanQ69L that are constitutively GTP-bound are used to dissect the pathway. Disruptions in the Ran cycle can affect transport efficiency and cell division.