| The nucleus is perhaps the most complex organelle of the cell. The wide range of functions of the cell nucleus and its molecular components include packaging and maintaining the integrity of the cellular genetic material, generating messages to the protein synthesis machinery of the cell, assembling ribosome precursors and delivering them to the cell cytoplasm, and many more. As a complex machine, the nucleus maintains a constant two-way flow of information with the surrounding cytoplasm, such as import and export of ions, small and large proteins and protein complexes, and ribonucleoprotein particles. These transport processes occur through the nuclear pore complexes which represent the selective gateways through the nuclear envelope, a major barrier that isolates the nucleus from the cytoplasm.
The nuclear envelope (NE) defines the boundary between nucleus and cytoplasm. It is formed by two juxtaposed lipid bilayer membranes, the outer one of which is contiguous with the endoplasmic reticulum. The outer and inner lipid bilayers are also connected continuously through the nuclear pores themselves, though their protein compositions differ. A matrix of filaments underlies the inner nuclear membrane, providing mechanical support and anchoring sites for the enclosed chromatin. In animal cells these filaments are composed largely of lamins, similar in structure to intermediate filaments. Aside from a few known exceptions associated with viral infection, all molecular exchange across the nuclear envelope takes place via the nuclear pores, whose number ranges from many tens to several thousand per nucleus. Thus RNAs and ribosomal subunits are exported to the cytoplasm, while proteins needed in the nucleus must be imported, and often reexported when their task there is done. Each pore is a large multi-protein complex, consisting of 30 or more distinct protein components in multiple copies. Its total molecular weight has been measured at 125 MDa for vertebrate cells, and about 60 MDa for yeast. Individual nuclear pores are thought to mediate traffic in both directions.
The functional task of the nuclear pore is to regulate entry to, and exit from, the nucleus. Specific pathways are discussed at greater depth in other chapters of this book. A degree of consensus has emerged in describing nuclear transport as a receptor-mediated translocation process. Molecular cargo is marked for import (or export) by the presence of peptide signals, which are then recognized by specific receptors that serve to usher the cargo across the pore. Models of translocation can been categorized into those that anticipate some form of micromechanical movement (for example iris-like closures) of the pore itself on one hand, or entirely biochemical sieves on the other. While deep modulation of calcium levels has a pronounced effect on nuclear pore structure in vitro, calcium depletion does not appear to be coupled to nuclear transport regulation in intact cells. The lack of intrinsic ATPase activity in the nuclear pore supports the second, nonmechanical class of models. |