Figure 261

Schematic drawing of the structure of the nuclear pore complex.

Each pore contains eight protein subunits arranged in an octagonal central framework at the periphery of the pore. These subunits form a nuclear pore complex that is inserted between two cytoplasmic and nuclear rings. Eight short protein fibrils protrude from the cytoplasmic ring into the cytoplasm. The nuclear ring anchors a basket assembled from eight thin filaments joined distally by a protein ring. The cylindrical central framework encircles the central pore, which acts as a close-fitting diaphragm.

either ribosomes or other protein complexes (transporters) captured during their passage through the pore at the time of fixation.

With special techniques, such as negative staining and high-voltage transmission electron microscopy, the nuclear pore exhibits additional structural detail. Eight mul-tidomain protein subunits arranged in an octagonal central framework at the periphery of each pore form a cylinder-like structure known as the nuclear pore complex (NPC). The NPC, whose total mass is estimated at 125 X 106 Da, is composed of about 50 different nuclear pore complex proteins collectively referred to as nucleo-ponns (Nup proteins). This central framework is inserted between two cytoplasmic and nuclear rings (Fig. 2.61). From the cytoplasmic ring, eight short protein fibrils protrude into the cytoplasm. The nucleoplasmic ring complex anchors a basket (or nuclear "cagewhich resembles a fish trap) assembled from eight thin 50-nm-long filaments joined distally by a 30- to 50-nm-diameter ring. The cylinder-shaped central framework encircles the central pore of the NPC, which acts as a close-fitting diaphragm or gated channel. In addition, each NPC contains one or more water-filled channels for transport of small molecules.

cytoplasmic ring subunit central framework protein fibril scaffold luminal subunit nucleoplasmic ring subunit lamina outer and inner nuclear membrane

The NPC mediates bidirectional nucleocytoplasmic transport

Various experiments have shown that the nuclear pore complex regulates the passage of proteins between the nucleus and the cytoplasm (Fig. 2.62). 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 RNAs, large proteins, and macromolecular complexes) depend for passage on the presence of an attached signal sequence called the nuclear localization signal. Labeled proteins destined for the nucleus then bind to a soluble cytosolic receptor called a nuclear import receptor that directs them from the cytoplasm to an appropriate NPC. They are then actively transported through the pore by a GTP energy-dependent mechanism. The NPC transports proteins as well as ribosomal subunits in their fully folded configuration.

• Ions and smaller water-soluble molecules (less than 9 Da) may cross the water-filled 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 diffuse, rather than the 70- to 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 by simple diffusion.

During cell division, the nuclear envelope is disassembled to allow chromosome separation and is later reassembled as the daughter cells form

In early 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.

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