Components and regulation of nuclear transport processes

Abstract

The spatial separation of DNA replication and gene transcription in the nucleus and protein translation in the cytoplasm is a uniform principle of eukaryotic cells. This compartmentalization imposes a requirement for a transport network of macromolecules to shuttle these components in and out of the nucleus. This nucleo-cytoplasmic transport of macromolecules is critical for both cell physiology and pathology. Consequently, investigating its regulation and disease-associated alterations can reveal novel therapeutic approaches to fight human diseases, such as cancer or viral infection. The characterization of the nuclear pore complex, the identification of transport signals and transport receptors, as well as the characterization of the Ran system (providing the energy source for efficient cargo transport) has greatly facilitated our understanding of the components, mechanisms and regulation of the nucleo-cytoplasmic transport of proteins in our cells. Here we review this knowledge with a specific emphasis on the selection of disease-relevant molecular targets for potential therapeutic intervention.

Keywords: anti-cancer therapy; anti-viral therapy; karyopherins; nuclear export; nuclear import; nuclear pore complex; nuclear trafficking.

Figure 1

Overall structure and molecular composition of the nuclear pore complexes (NPCs). (A) General structural features of the NPC. (B) A schematic model of the NPC. In this model, the NPC is divided into several groups according to their location and structural characteristics. The symmetrical core is composed of membrane‐anchored POMS (transmembrane ring), channel Nups (central FG‐Nups) and scaffold Nups composed by adaptor Nups (inner and linker Nups) and coat Nups (outer ring). Asymmetric parts of the pore are the nuclear FG‐Nups and the basket plus the cytoplasmic FG‐Nups and filaments. (C) The yeast and vertebrate homolog Nups that are known to constitute each NPC substructure are listed. Symmetric Nups are equally distributed on the cytoplasmic and nucleoplasmic parts of the NPC and form the core region. Asymmetric Nups form the nuclear basket and the cytoplasmic filaments. They serve as docking sites for transport factors and include associated mRNA export factors. See the main text for more information.

Figure 2

Schematic overview of Ran‐dependent nucleo‐cytoplasmic transport. Nuclear export. CRM1 exports a great part of NES‐containing protein. Nuclear import. Importin‐α (Imp‐α)/importin‐β (Imp‐β) heterodimer (designated as α and β) and karyopherin‐β2 mediate the import of NLS‐containing proteins. See the main text for details.