On the Role of the Channel Nucleoporins in Nuclear Transport

Abstract

The nuclear pore complex (NPC) facilitates transport of a large diversity of cargoes, including proteins, mRNA protein complexes, and ribosomal subunits. Three of its proteins line the central transport channel: Nup58, Nup54, and Nup62. These channel nups are essential to achieve significant transport rates through the NPC. Recently, several x-ray structures of the channel nups have been determined. Furthermore, a cryo-electron tomography structure of the NPC was determined, and the x-ray structures were docked into the electron microscopy map, yielding a composite structure of the NPC. These advances provide insight into the organization of the channel nups in the NPC transport channel, the FG-repeat permeability barrier, and the mechanism of active transport. They provide a foundation to investigate in the future whether the NPC scaffold is static, and merely serves to provide anchorage sites for FG-repeat domains, or whether multiple structural conformations of the NPC scaffold are formed. It will also be important to investigate how the presence of FG-repeats, which make up a significant portion of the NPC mass, and their interactions with transport receptors modulate the NPC scaffold and how this affects nuclear transport rates. It also needs to be established how distinct physiological states, such as cell proliferation, developmental stages, cell quiescence, cancer, or viral infections, modulate the structure and composition of the NPC transport channel to adjust transport rates to cellular demands.