Nuclear import and export: transport factors, mechanisms and regulation.

Abstract

Molecules enter and exit the nucleus of eukaryotic cells through aqueous channels formed in the nuclear envelope by nuclear pore complexes (NPC). Proteins entering or leaving the nucleus use nuclear localization signals (NLSs), or nuclear export signals (NESs), respectively. Different types of NLSs and NESs are specifically recognized directly, or indirectly via adapters, by transport receptors. In recent years, many transport receptors, adapters, and the specific cargoes they carry into or out of the nucleus have been identified, revealing an increasing level of complexity. All the transport receptors identified are members of the same family and have in common the ability to shuttle between the nucleus and cytoplasm, and to interact with RanGTP and with nucleoporins at the NPC. The GTPase Ran regulates the interaction between receptors and cargoes, or adapters, and is crucial in providing directionality to nuclear import and export. One of the challenges for the future will be establishing the mechanisms of translocation through the NPC of receptors together with their cargoes. Nuclear import and export of many cargoes is regulated. The molecular mechanisms of regulation of nucleocytoplasmic transport during cell growth, development, viral infections, and different diseases constitute important areas of investigation.