Structure, dynamics and function of nuclear pore complexes

Abstract

Nuclear pore complexes are large aqueous channels that penetrate the nuclear envelope, thereby connecting the nuclear interior with the cytoplasm. Until recently, these macromolecular complexes were viewed as static structures, the only function of which was to control the molecular trafficking between the two compartments. It has now become evident that this simplistic scenario is inaccurate and that nuclear pore complexes are highly dynamic multiprotein assemblies involved in diverse cellular processes ranging from the organization of the cytoskeleton to gene expression. In this review, we discuss the most recent developments in the nuclear-pore-complex field, focusing on the assembly, disassembly, maintenance and function of this macromolecular structure.

Figure 1. Nuclear pore complex (NPC) structure and composition

(a) Schematic illustration of the NPC structure (b) Predicted localization of subcomplexes and nucleoporins within the NPC. The members of the Nup214 complex (Nup214, Nup88), Nup98 complex (Nup98, Rae1), Nup107–160 complex (Nup160, Nup133, Nup107, Nup96, Nup75, Nup43, Nup37, Sec13, Seh1), Nup62 complex (Nup62, Nup58, Nup54, Nup45), and Nup93–205 complex (Nup205, Nup188, Nup155, Nup93, Nup35) are enclosed in the same box. Green lines show the location of the three transmembrane nucleoporins, red lines the location of peripheral components and blue lines indicate the location of scaffold subcomplexes.

Figure 2. NPC assembly during mitosis and interphase

Mitotic NPC assembly occurs concomitantly with the formation of new nuclear envelopes (NEs) around chromatin. During this time, NPCs assemble by recycling subcomplexes that were dispersed into the cytoplasm during NPC and NE breakdown. Note that, during mitosis, the cytoplasmic and nuclear contents are mixed together. Mitotic assembly is a step-wise process that begins with the recruitment of structural nups to chromatin during early anaphase. During interphase, by contrast, NPCs assemble into an intact NE when the nucleus and cytoplasm are physically separated. During this process, NPCs utilize newly synthesized nucleoporins present on both sides of the nuclear envelope.

Figure 3. Importin β and RanGTPase regulation of NPC assembly

(a) During mitosis, Importin β binds and sequesters the Elys/Mel-28 nucleoporin (Mel-28), preventing its interaction with chromatin. When the Importin-β—Mel-28 complexes are in the proximity of DNA, where there is a high concentration of RanGTP due to the chromatin association of the Ran GDP—GTP exchange factor (regulator of chromosome condensation, RCC1), RanGTP binds to the transport receptor, releasing Mel-28 and allowing it to bind to chromatin. Following the same mechanism, the Importin-β-bound Nup107–160 complex is released by RanGTP in the proximity of DNA and recruited to chromatin through Mel-28. The chromatin-bound Nup107–160 complex can then recruit other nucleoporins in a step-wise manner. (b) NPC assembly during interphase requires the RanGTP-dependent release of the Nup107–160 complex from Importin β on the cytoplasmic and nuclear side of the NE. How the released complexes coordinate the formation of a functional NPC from both sides of the nuclear envelope is still unclear.