The Nuclear Pore Complex and Nuclear Transport

The nuclear pore complex (NPC) is an essential gateway between the cell nucleus and the cytoplasm. The NPC is formed by multiple copies of ∼30 different proteins called nucleoporins, which can be divided into scaffold, membrane-anchored and barrier components. Thousands of phenylalanine-glycine (FG) repeats, found in barrier nucleoporins, interact to form the selective permeability barrier of the NPC channel. Shuttling nuclear transport receptors are able to interact with these FG repeats and mediate the passage of large macromolecular cargoes through the barrier. Combinations of shuttling receptors, their adaptors and localisation signals in cargo molecules define a wide array of nuclear import and export pathways. Recent research has pointed to some dynamic features in NPC components, as well as a number of nucleoporin-related human diseases which are characterised by highly cell-type-specific phenotypes. Key Concepts The nuclear pore complex (NPC) is a massive and elaborate structure formed by multiple copies of ∼30 different nucleoporins. The selective permeability barrier of the NPC is formed by hydrophobic interactions among FG repeats found in a large group of nucleoporins. Ions and small molecules are able to passively diffuse through the aqueous central channel of the NPC. Macromolecules transported through the NPC must contain specific targeting signals for nuclear import and nuclear export. Targeting signals are recognised by shuttling transport receptors which mediate the passage through the NPC channel by interacting with FG repeats. A small number of inherited diseases have been linked to mutations in human nucleoporins and are characterised by cell-type-specific phenotypes. Keywords: nuclear pore complex; nucleoporins; nuclear envelope; nuclear pore scaffold; nuclear transport; FG repeats; karyopherins