karyopherinek

Karyopherins are a family of nuclear transport receptors that mediate the selective movement of proteins and ribonucleoprotein particles through the nuclear pore complex (NPC) between the cytoplasm and the nucleus. They include import receptors (importins) and export receptors (exportins). The best characterized exportin is CRM1/XPO1, while the import machinery involves importin-β1 and its partners, such as importin-α (an adaptor).

Mechanism: Cargo proteins bearing a nuclear localization signal (NLS) are captured by importins; cargoes bearing a nuclear export signal (NES) bind exportins in combination with Ran-GTP to form cargo–receptor–Ran complexes. These complexes translocate through the NPC. In the nucleus, Ran-GTP binding promotes cargo release for importins; for exportins, Ran-GTP binding enables cargo binding, and hydrolysis of Ran-GTP to Ran-GDP in the cytoplasm triggers dissociation and receptor recycling.

Structure: Many karyopherins consist of HEAT repeats that form elongated, flexible structures suitable for diverse cargo binding and interactions with the NPC and Ran.

Biological significance: Karyopherins regulate the localization of transcription factors, chromatin modifiers, ribonucleoprotein particles, and other regulators, influencing processes such as cell cycle progression, development, and stress responses. Dysfunction or altered expression is linked to cancer, viral infections, and neurodegenerative diseases. Pharmacological targeting of CRM1, for example with selinexor, is explored in cancer therapy.

Evolution and redundancy: In eukaryotes, a family of several karyopherins exists with varying cargo specificities and tissue distributions. They operate in concert with the Ran GTPase system to ensure directionality and efficiency of nuclear transport.