nucleoporins

Nucleoporins, or Nups, are a family of proteins that make up the nuclear pore complex (NPC), the large assembly embedded in the nuclear envelope that regulates traffic between the nucleus and cytoplasm. In most eukaryotes, the NPC comprises around 30 to 50 distinct nucleoporins organized into a symmetric structure that includes a structural scaffold, a central transport channel, and membrane anchors.

Nucleoporins fall into several functional classes. Scaffold nucleoporins form the ring-like framework that gives the NPC its shape and stability. Transmembrane nucleoporins anchor the complex to the nuclear envelope and help coordinate assembly and membrane interactions. A large subset, the FG-repeat nucleoporins, lines the central channel with phenylalanine-glycine repeats and creates a selective permeability barrier that allows small molecules to diffuse while restricting larger macromolecules unless escorted by transport receptors.

Nucleocytoplasmic transport through the NPC is mediated by karyopherins, including importins and exportins, which recognize cargoes bearing nuclear localization signals (NLS) or nuclear export signals (NES). These receptors interact with FG repeats to ferry cargo through the pore. Directionality is driven by the Ran GTPase gradient, with RanGTP higher in the nucleus to promote cargo release and recycling of transport receptors.

NPCs are embedded in the nuclear envelope with eightfold symmetry. Their assembly and turnover are coordinated with the cell cycle, and NPC numbers are tightly regulated in many cells. Defects or dysregulation of nucleoporins have been linked to human disease, including neurodevelopmental disorders, kidney disease, and cancer. For example, NUP62 mutations are associated with pontocerebellar hypoplasia, NUP93 mutations with nephrotic syndrome, and NUP98 fusions are recurrent in leukemias.