Mechanisms and signals for the nuclear import of proteins

Abstract

In eukaryotes, the nuclear membrane provides a physical barrier to the passive diffusion of macromolecules from and into the cytoplasm. Nucleocytoplasmic traffic occurs through highly specialized structures known as nuclear pores, and involves the participation of a special class of transport proteins. Active transport across the nuclear pores is an energy-dependent process that relies on the activity of Ran-GTPases both in the nuclear and cytoplasmic compartments. Nuclear import of proteins is an essential step in regulating gene expression and the replication cycle of several viruses. In this review, the key mechanisms, pathways, and models underlying the transport of proteins across nuclear pores are analysed.

Keywords: Nuclear pore complex; importin; nuclear localization signal; nuclear transport..

Fig. (1)

Schematic view of the nuclear pore complex. The crosssection of the nuclear ring, central structure, and cytoplasmic ring are displayed on the top, middle, and bottom of the figure, respectively.

Fig. (2)

Schematic representation of protein nuclear import pathways. I- Import of UsnRNPs is mediated by importin-β which associates with the SMN complex coupled to UsnRNAs; II- The RanGTP gradient regulates the shuttling of importin-β between the nucleus and the cytoplasm; III- The direct interaction of importin-β with cargos promotes translocation through nuclear pores of several proteins; IV- Importin-α recognizes the NLS in the cargos and interacts with importin-β through the IBB domain to promote nuclear import; V- The nuclear import of Ran-GDP is mediated by the nuclear transport factor NTF2.