Nuclear export signals: small domains with large impact

Abstract

Nucleocytoplasmic traffic is one of the hallmarks of the eukaryotic cell. To a large extent, this process is mediated by nuclear import and export receptors. Study of nuclear import and export has had wide implications for many cellular processes including basic cell metabolism, cellular differentiation and disease. In this thesis I have studied the nuclear export receptor CRM1/exportin1 and its interaction with various transport substrates and the nuclear pore complex (NPC), the supramolecular structure through which receptor-mediated nucleocytoplasmic transport takes place. CRM1 interacts with its substrate through the nuclear export signal (NES) and I have identified a novel type NES, the supraphysiological NES (supraNES). This is a synthetic peptide NES that binds CRM1 with an unusual high affinity. Interestingly, we found that supraNESs do not only exist as synthetic peptides, but are present in certain viruses, where they are required for export of the viral particle from the nucleus. The currently emerging supraNESs in other viruses and the hypothesis that supraNESs could be responsible for export of large cargo in general will be discussed.