Various experiments have shown that the NPC regulates the passage of proteins between the nucleus and the cytoplasm. The significance of the NPC can be readily appreciated, as the nucleus does not carry out protein synthesis. Ribosomal proteins are partially assembled into ribosomal subunits in the nucleolus and are transported through nuclear pores to the cytoplasm. Conversely, nuclear proteins, such as histones and lamins, are produced in the cytoplasm and are transported through nuclear pores into the nucleus. Transport through the NPC largely depends on the size of the molecules:  Large molecules (such as large proteins and macromolecular complexes) depend on the presence of an attached signal sequence called the nuclear localization signal (NLS) for passage through the pores. Labeled NLS proteins destined for the nucleus then bind to a soluble cytosolic receptor called a nuclear import receptor (importin) that directs them from the cytoplasm to an appropriate NPC.
FIGURE 3.7 • Electron micrograph of the nuclear envelope.
Note the visible nuclear pore complexes (arrows) and the two membranes that constitute the nuclear envelope. At the periphery of each pore, the outer and inner membranes of the nuclear envelope appear continuous. 30,000.
They are then actively transported through the pore by a GTP energy-dependent mechanism. An export of proteins and RNA from the nucleus is similar to the import mechanism into the nucleus. Proteins that possess the nuclear export sequence (NES) bind in the nucleus to exportin (a protein that moves molecules from nucleus into cytoplasm) and to a GTP molecule. Protein–exportin–GTP complexes pass through NPC into the cytoplasm where GTP is hydrolyzed and the NES protein is released. The NPC transports proteins, all forms of RNA, as well as ribosomal subunits in their fully folded configurations.
 Ions and smaller water-soluble molecules (less than 9 daltons) may cross the water-flled channels of the NPC by simple diffusion. This process is nonspecific and does not require nuclear signal proteins. The effective size of the pore is about 9 nm for substances that cross by diffusion rather than the 70to 80-nm measurement of the pore boundary. However, even the smaller nuclear proteins that are capable of diffusion are selectively transported, presumably because the rate is faster than simple diffusion.
During cell division, the nuclear envelope is disassembled to allow chromosome separation and is later reassembled as the daughter cells form.
In late prophase of cell division, enzymes (kinases) are activated that cause phosphorylation of the nuclear lamins and other lamina-associated proteins of the nuclear envelope. After phosphorylation, the proteins become soluble, and the nuclear envelope disassembles. The lipid component of the nuclear membranes then disassociates from the proteins and is retained in small cytoplasmic vesicles. The replicated chromosomes then attach to the microtubules of the mitotic spindle and undergo active movement.
Reassembly of the nuclear envelope begins in late anaphase, when phosphatases are activated to remove the phosphate residues from the nuclear lamins. During telophase, the nuclear lamins begin to repolymerize and form the nuclear lamina material around each set of daughter chromosomes. At the same time, vesicles containing the lipid components of the nuclear membranes and structural membrane protein components fuse, and an envelope is formed on the surface of the already-reassembled nuclear lamina. By the end of telophase, formation of a nuclear envelope in each daughter cell is complete.
Nucleoplasm is the material enclosed by the nuclear envelope exclusive of the chromatin and the nucleolus.