Eksportin

Eksportin is a family of transport receptors, part of the larger karyopherin superfamily, that mediate the export of proteins and ribonucleoprotein particles from the cell nucleus to the cytoplasm via the nuclear pore complex. Cargo molecules typically contain a leucine-rich nuclear export signal (NES) that is recognized by specific eksportin proteins in conjunction with RanGTP.

In the nucleus, eksportin binds to RanGTP and the NES-containing cargo to form a trimeric export complex. This complex then translocates through the nuclear pore into the cytoplasm. In the cytoplasm, RanGTP is hydrolyzed to RanGDP, triggering dissociation of the complex and release of the cargo. The eksportin and RanGDP are recycled back to the nucleus to participate in additional rounds of transport. The RanGTP gradient across the nuclear envelope provides the directionality of export.

Several eksportins are well characterized. Exportin-1 (CRM1) exports a broad range of regulatory proteins, including tumor suppressors and cell cycle regulators. Exportin-5 exports precursor microRNAs (pre-miRNAs) from the nucleus to the cytoplasm. Exportin-T exports tRNAs, and Exportin-4 transports a subset of proteins and nucleic acid–protein complexes. The specificity of each eksportin for particular cargoes contributes to the regulation of gene expression and cellular signaling.

Dysregulation of eksportin-mediated export is associated with diseases, notably cancer, where mislocalization of tumor suppressors or other regulatory proteins can occur. Inhibitors of eksportins, such as leptomycin B targeting Exportin-1 or clinically developed Selective Inhibitors of Nuclear Export (SINE) compounds like selinexor, are studied for therapeutic potential.