The nuclear envelope. The NE is an integral part of the ER-membrane network (in blue-green). The inner nuclear membrane (INM) and outer nuclear membrane (ONM) connect at sites of NPCs (green barrels) where the membrane curves as it surrounds the NPC. The ONM is continuous with the peripheral ER. The NE contains a variety of proteins that are embedded in the INM (purple) or the ONM (light blue). Most ONM proteins are also found in the peripheral ER. INM proteins can interact with the underlying nuclear lamina (dark blue), with ONM proteins or with chromatin (red), often through linker proteins (yellow). For a detailed description of the various proteins associated with the NE see recent reviews (Crisp and Burke, 2008; Guttinger et al., 2009).

Open and closed mitosis. (A) Open mitosis is so named because of the disassembly of the NE (green) during mitosis, which opens up the nucleus and exposes the chromosomes (red) to the cytoplasm. The NE breaks down early in mitosis, as the chromosomes condense, allowing microtubules (purple filaments) that emanate from centrosomes (purple structures) to associate with the chromosomes. During mitosis, the chromosomes congress to the metaphase plate, followed by separation of sister chromatids in anaphase. The NE begins to reassemble shortly thereafter, in telophase. Once the NE is completely assembled, the nucleus expands and the chromosomes return to their decondensed state in interphase. (B) Closed mitosis is so named because of the persistence of the NE throughout the cell cycle, such that the nucleus never `opens' to the cytoplasm. This type of mitosis occurs in certain fungi (such as budding yeast, shown here), in which the centrosome equivalents, called the spindle-pole bodies (purple), are embedded in the NE. During closed mitosis, the spindle-pole bodies nucleate microtubules within the nucleus, but as the DNA (red) begins to segregate, the nucleus has to elongate. Once segregation is completed, the nucleus divides and re-establishes a spherical shape. Note that, in budding yeast, chromosome condensation and a metaphase plate are not visible by microscopy.

Variation in nuclear shape. The nuclei of most cells, such as those of the C. elegans embryo (A), are either oval or round. However, various cell types or conditions display non-round nuclei. Shown are the nuclei of neutrophils (B), of cells from a patient with HGPS (C) and of cells from a 96-year-old individual (D, right panel) compared with nuclei of cells from a 9-year-old individual (D, left panel). Visualization of nuclei was performed with a GFP-tagged NPC component, NPP-1 (A), an antibody specific for lamin B (B), an antibody specific for emerin (a lamina-associated protein, C) and an antibody specific for lamin A and lamin C (D). The image in B was reprinted with permission from Ada Olins and Donald Olins (Olins and Olins, 2005). The image in C was reprinted with permission from Goldman (Goldman et al., 2004). The images in D were provided by Tom Misteli and Paola Scaffdi (NCI, Bethesda MD) (see also Scaffidi and Misteli, 2006). Nuclei are not shown to scale.

Nuclear-envelope assembly. (A) A general view of NE assembly. Initial contacts with the chromatin (black and gray bars) are thought to be made by tips of ER tubules (blue-green). These tubules then flatten to form an intact NE, which then expands and the chromosomes decondense. (B) A closer view of NE assembly. The ER tubules are decorated with chromatin-binding NE proteins (shown in multiple colors), which are thought to mediate the interaction between the membrane and the chromatin (black). These proteins are eventually located on the inner nuclear membrane. As NE assembly progresses, the membrane flattens onto the chromatin (note the progressive accumulation of chromatin-binding proteins at the interface between the membrane and chromatin). Because the ER membrane is one continuous membrane, the gap between two adjacent tubules will be filled by this membrane-flattening process.

The formation of micronuclei. (A) When all chromosomes (black) congress properly to the metaphase plate via the mitotic spindle (purple), a single NE (blue) is able to form around all of the DNA in telophase (top), resulting in a single nucleus in the ensuing interphase. However, when some DNA remains separate from the metaphase plate, such as lagging chromosomes that are not associated with the spindle, then that DNA fails to become encapsulated into the same NE and a micronucleus forms. (B) Micronucleus formed adjacent to the nucleus of a human buccal cell. DNA is shown in dark blue, and alpha-satellite DNA, which marks centromeres, the chromosomal sites of attachment to spindle microtubules, is shown in light blue. Note that the micronucleus does not contain alpha-satellite sequences, suggesting that the micronucleus was formed because of a failure in attaching to the spindle. Reprinted from Norppa and Falck (Norppa and Falck, 2003) with permission from Oxford University Press.

The limited flat membrane hypothesis. During closed mitosis (A), excess membrane in the form of sheets results in a failure to reform a spherical nucleus, suggesting that limited membrane availability drives nuclear shape change at the end of mitosis. During open mitosis (B), excess flat membrane might facilitate the formation of multiple nuclei that collectively have the same volume as a single nucleus that would form under conditions of limited flat membrane availability. The NE is shown in green and the DNA in red. See text for more details.