Border control at the nucleus: biogenesis and organization of the nuclear membrane and pore complexes

Abstract

Over the last decade, the nuclear envelope (NE) has emerged as a key component in the organization and function of the nuclear genome. As many as 100 different proteins are thought to specifically localize to this double membrane that separates the cytoplasm and the nucleoplasm of eukaryotic cells. Selective portals through the NE are formed at sites where the inner and outer nuclear membranes are fused, and the coincident assembly of approximately 30 proteins into nuclear pore complexes occurs. These nuclear pore complexes are essential for the control of nucleocytoplasmic exchange. Many of the NE and nuclear pore proteins are thought to play crucial roles in gene regulation and thus are increasingly linked to human diseases.

Figure 1. De Novo NPC Biogenesis

Distinct steps in the sequential self-assembly pathway are shown (supporting references are cited in the text). (A) At the closed nuclear envelope (NE), specific Nups are assembled into subcomplexes and recruited to preassembly sites on the inner nuclear membrane (INM)or outer nuclear membrane (ONM). (B) The RanGTPase is required on both sides of the NE to mediate nuclear localization via preexisting NPCs and to release assembly factors and/or Nups. (C) Proteins at preassembly sites on the INM and ONM mediate close apposition of the membranes. Poms are shown here as one possible mediator of this apposition; other possible mediators are discussed in the text. (D) Pore formation requires that the luminal leaflets of the INM and ONM resolve and fuse. (E) Nascent pore membrane curvature could be transiently stabilized by the reticulons (RTNs). (F) Recruitment of Nup subcomplexes results in a stable membrane coat and linkage of the Poms to the central ring Nups via yNup170/157 and yNup53/59. (G) Assembly of the peripheral Nups forms the filamentous cytoplasmic and nuclear structures, with the permeability barrier from FG domains and a central 9 nm aqueous channel.

Figure 2. Cell Cycle Dynamics of the Nuclear Envelope Border

Nuclear envelope breakdown (NEBD) and nuclear envelope (NE) formation are both observed in cultured human osteosarcoma (U2OS) cells as they progress through the cell cycle. The NE is visualized by Pom121-GFP (green), whereas the chromatin is visualized by histone H2B-cherry (red). Image courtesy of Jesse Vargas.