The nuclear pore: at the crossroads.

The nuclear pore complex is at the crossroads of macromolecular traffic across the nuclear envelope. Our knowledge of the mechanism whereby nuclear transport is mediated by the nuclear pore complex is also at a crossroads; a molecular understanding of this process has major implications for applied medical sciences. This becomes obvious with the realization that nuclear proteins are synthesized in the cytoplasm and yet function in the nucleus, and that RNA is transcribed in the nucleus but translated in the cytoplasm. Thus, control of macromolecular traffic across the nuclear membrane is an important means for altering the levels and activities of such molecules as steroid hormone receptors, transcription factors, and enzymes involved in DNA replication. Nuclear proteins have been found to contain nuclear localization sequences (NLS) rich in basic amino acids, which target them for transport through the nuclear pore to the nucleus. It is also clear that a group of novel glycoproteins having a unique carbohydrate modification are required for transport across the nuclear pore complex. However, the mechanism by which the NLS is recognized to mediate transport across the nuclear envelope is poorly understood. It is the aim of this brief review to attempt a synthesis of what is known of this mechanism and what may be newly inferred on the basis of current experimental data.