RanGEF

Ran guanine nucleotide exchange factor, or RanGEF, designates a family of proteins that activate the small GTPase Ran by catalyzing the exchange of GDP for GTP. In cells, Ran cycles between GDP- and GTP-bound forms, and RanGEFs facilitate GDP release so Ran can bind GTP, which is more abundant in the cytoplasm. This exchange reaction helps establish and maintain the Ran-GTP gradient that underpins many nucleocytoplasmic processes.

The best-characterized RanGEF is RCC1 (Regulator of Chromosome Condensation 1). RCC1 is chromatin-associated, binding to chromosomes and generating RanGTP on chromatin. This activity concentrates RanGTP in the nucleus during interphase and mitosis, providing directional energy for the transport of proteins and RNAs through nuclear pore complexes and coordinating spindle functions during cell division.

In mammals and other eukaryotes, additional RanGEFs have been identified beyond RCC1. These include RCC1-like proteins and, in some systems, RCC2 (also known as TD-60), which localizes to kinetochores and contributes to mitotic spindle assembly and function. Different RanGEFs can localize to distinct cellular compartments, allowing regulation of Ran activity in multiple contexts.

Biological roles of RanGEFs are closely tied to the Ran cycle. By generating RanGTP in specific locations, RanGEFs drive nucleocytoplasmic transport, proper mitotic spindle formation, and nuclear envelope reassembly after mitosis. The activity and localization of RanGEFs are regulated by interactions with chromatin, membranes, and other regulatory proteins, ensuring that Ran signaling is coordinated with cell cycle progression and cellular architecture.

Overall, RanGEFs are essential regulators of Ran activity, and their proper function supports fundamental cellular processes that depend on a controlled RanGTP gradient.