Protein translocation: Nuclear export –  out of the dark

Nuclear pore complexes serve as the gateways between the nucleus and cytoplasm, and control the movement of macromolecules between these two subcellular compartments. Although microinjection studies have shown that the nuclear pore complex can allow free diffusion of globular proteins up to about 50 kDa, the import of most nuclear proteins, as well as the export of all classes of RNA, are both energyand temperature-dependent, indicating active transport through the nuclear pore complex rather than passive diffusion [1,2]. Some proteins do not simply move into the nucleus and stay there — they shuttle, at various rates, between the nucleus and cytoplasm. These include several nucleolar proteins, steroid hormone receptors, ‘heat-shock cognate’ protein (hsc70), the catalytic subunit of cAMP-dependent protein kinase (cAPK), the human immunodeficiency virus 1 (HIV-1) Rev protein and some of the heterogeneous (hn)RNP proteins. Our understanding of nuclear export has lagged well behind that of nuclear import, but now studies of ‘shuttling’ proteins have led to the elucidation of specific signals for nuclear protein export, as well to the characterization of a unique region of the hnRNP protein A1 that mediates both nuclear import and export [3–5].