karyopherinmediated

Karyopherin-mediated transport refers to the movement of proteins, ribonucleoproteins, and other macromolecules between the nucleus and cytoplasm through nuclear pore complexes, driven by karyopherin receptors, also known as importins and exportins. The karyopherin family includes receptors that recognize cargo via nuclear localization signals (NLS) for import or nuclear export signals (NES) for export. Cargo recognition can occur directly or through adaptor proteins that bridge the interaction.

The mechanism relies on a running Ran GTPase gradient across the nuclear envelope. For import, cytoplasmic cargo bearing an NLS binds to import receptors (such as importin-α/β), facilitating docking at the nuclear pore and translocation into the nucleus. In the nucleus, RanGTP binds to the receptor, causing release of the cargo. The receptor-RanGTP complex then cycles back to the cytoplasm, where GTP hydrolysis converts RanGTP to RanGDP, freeing the receptor. For export, cargo with an NES binds to exportins in the presence of RanGTP within the nucleus to form a cargo–exportin–RanGTP complex, which is transported to the cytoplasm. Hydrolysis of RanGTP to RanGDP leads to cargo release and receptor recycling.

Major examples include importins of the importin-β family (with adapters like importin-α) and exportins such as CRM1/XPO1. Karyopherin-mediated transport is essential for the nuclear import of transcription factors, DNA replication and repair factors, ribosomal subunits, and various RNA-related proteins, as well as for maintaining cellular homeostasis. Disruptions in this pathway are linked to a range of diseases, including cancer and neurodegenerative conditions.