eksportinmediated

Exportin-mediated transport refers to the process by which exportins, a family of nuclear transport receptors, mediate the export of selected proteins and RNAs from the nucleus to the cytoplasm through the nuclear pore complex. Cargo molecules typically contain nuclear export signals (NES) that are recognized by exportins in the presence of RanGTP.

Mechanism: In the nucleoplasm, exportins bind NES-containing cargo in a complex with RanGTP. The complex translocates through the NPC to the cytoplasm. In the cytoplasm, RanGAP stimulates hydrolysis of RanGTP to RanGDP, causing dissociation of the complex and release of cargo. The exportin then recycles back to the nucleus to participate in new rounds of transport. The RanGTP concentration gradient across the nuclear envelope provides directionality.

Examples and relevance: The best characterized exportin is exportin-1 (XPO1, also known as CRM1). It exports many regulatory proteins, including tumor suppressors like p53 and cell-cycle regulators. Exportin-5 (XPO5) exports precursor microRNAs in complex with RanGTP and its cargo. Other exportins like XPO4 and XPO7 transport various proteins. Inhibition of exportins, notably XPO1, by drugs such as leptomycin B (a laboratory tool) and selinexor (a clinically investigated cancer therapy) can alter localization and activity of cargo proteins, with potential therapeutic effects.

Clinical and biological significance: Proper exportin function is essential for cell cycle control, gene expression, and stress responses. Dysregulation of exportin-mediated transport can contribute to disease by mislocalizing key regulatory proteins. Research continues to map cargo repertoires and to develop selective exportin inhibitors as therapeutic strategies.