The life cycle of the metazoan nuclear envelope

Abstract

The nuclear envelope is a double-layered membrane that encloses the nuclear genome and transcriptional machinery. In dividing cells of metazoa, the nucleus completely disassembles during mitosis, creating the need to re-establish the nuclear compartment at the end of each cell division. Given the crucial role of the nuclear envelope in gene regulation and cellular organization, it is not surprising that its biogenesis and organization have become active research areas. We will review recent insights into nuclear membrane dynamics during the cell cycle.

Figure 1

NE dynamics during the cell cycle. Changes in the organization of the NE throughout open mitosis are shown in representative live-cell images and schematic illustrations. In live-cell images, ER and NE membranes are labeled with Sec61β(aa1−65)GFP (green), microtubules are labeled with α-tubulin-mcherry (red) and chromatin is stained with Hoechst 33342 (blue). Interphase: During interphase the NE completely surrounds the nucleus and is punctuated by nuclear pore complexes (NPC), which are transport channels present where the inner and outer nuclear membrane (INM, ONM) fuse. Distinct transmembrane proteins are present in the INM that bind to the nuclear lamin, a protein meshwork found within the nucleus, and chromatin. The ONM forms a continuous lipid bilayer with the ER, sharing many of the ER-associated proteins. Prophase: NE breakdown is initiated during prophase, when many on the constituents of the NE and lamina are phosphorylated to disrupt the protein-protein interactions. This, along with microtubule tearing of the NE (arrows) rapidly exposes the chromatin to the forming spindle. Metaphase: By metaphase the membranes of the NE have completely redistributed into the ER, clearing all membranes from the chromosomes. Soluble proteins of the NE and lamina are distributed mainly through the cytoplasm. Anaphase: Late in anaphase, NPC components and ER tubule tips are targeted to the segregated chromosomes, likely by dephosphorylation of the proteins involved in these targeting processes. Telophase: In telophase membranes expand around the chromosomes and NPC continues to assemble.