Nuclear pore complexes: guardians of the nuclear genome.

Eukaryotic cell function depends on the physical separation of nucleoplasmic and cytoplasmic components by the nuclear envelope (NE). Molecular communication between the two compartments involves active, signal-mediated trafficking, a function that is exclusively performed by nuclear pore complexes (NPCs). The individual NPC components and the mechanisms that are involved in nuclear trafficking are well documented and have become textbook knowledge. However, in addition to their roles as nuclear gatekeepers, NPC components-nucleoporins-have been shown to have critical roles in chromatin organization and gene regulation. These findings have sparked new enthusiasm to study the roles of this multiprotein complex in nuclear organization and explore novel functions that in some cases appear to go beyond a role in transport. Here, we discuss our present view of NPC biogenesis, which is tightly linked to proper cell cycle progression and cell differentiation. In addition, we summarize new data suggesting that NPCs represent dynamic hubs for the integration of gene regulation and nuclear transport processes.

The role of the nuclear envelope in cellular organization.

Over the last years it has become evident that the nuclear envelope (NE) is more than a passive membrane barrier that separates the nucleus from the cytoplasm. The NE not only controls the trafficking of macromolecules between the nucleoplasm and the cytosol, but also provides anchoring sites for chromosomes and cytoskeleton to the nuclear periphery. Targeting of chromatin to the NE might actually be part of gene expression regulation in eukaryotes. Mutations in certain NE proteins are associated with a diversity of human diseases, including muscular dystrophy, neuropathy, lipodistrophy, torsion dystonia and the premature aging condition progeria. Despite the importance of the NE for cell division and differentiation, relatively little is known about its biogenesis and its role in human diseases. It is our goal to provide a comprehensive view of the NE and to discuss possible implications of NE-associated changes for gene expression, chromatin organization and signal transduction.