The selective permeability barrier in the nuclear pore complex

Abstract

The nuclear pore complex (NPC) mediates the shuttle transport of macromolecules between the nucleus and cytoplasm in eukaryotic cells. The permeability barrier formed by intrinsically disordered phenylalanine-glycine-rich nucleoporins (FG-Nups) in the NPC functions as the critical selective control for nucleocytoplasmic transport. Signal-independent small molecules (< 40 kDa) passively diffuse through the pore, but passage of large cargo molecules is inhibited unless they are chaperoned by nuclear transport receptors (NTRs). NTRs are capable of interacting with FG-Nups and guide the cargos to cross the barrier by facilitated diffusion. The native conformation of the FGNups permeability barrier and the competition among multiple NTRs interacting with this barrier in the native NPCs are the 2 core questions still being highly debated in the field. Recently, we applied high-speed super-resolution fluorescence microscopy to map out the natural structure of the FGNups barrier and determined the competition among multiple NTRs as they interact with the barrier in the native NPCs. In this extra-view article, we will review the current understanding in the configuration and function of FG-Nups barrier and highlight the new evidence obtained recently to answer the core questions in nucleocytoplasmic transport.

Importin β1 targeting by hepatitis C virus NS3/4A protein restricts IRF3 and NF‐κB signaling of IFNB1 antiviral response

“…NPCs are ~60 to 120 MDa structures involved in the trafficking of macromolecules between the nucleus and the cytoplasm that are composed of at least 30 different Nups . These include the transmembrane Nups (POMs) that anchor to the NPC in the nuclear envelope, structural Nups that form the skeleton of the NPC, and the intrinsically disordered Nups that constitute the permeability barrier with their disordered phenylalanine‐glycine‐rich regions (FG‐Nups).…”

Nuclear networking

“…These channels are occupied by nuclear pore complexes (NPCs), massive multiprotein assemblies that regulate the back and forth movement of macromolecules across the NE. 2 As with the NE as a whole, NPCs are also highly conserved. Electron microscopic studies have revealed a core structure displaying eightfold radial symmetry.…”

The roles of the nuclear pore complex in cellular dysfunction, aging and disease

“…RanGap1, an NPC binding protein with known roles in nucleocytoplasmic transport, was also found to have increased expression after injury. Expression of the nucleoporins surprisingly shifted from the classical perinuclear pattern to an intranuclear pattern [80]. The expression pattern of other nucleoporins was not examined and these experiments are still preliminary, but the possible role of nucleoporins in the resolution or pathology of brain injuries is exciting.…”