Regulation of nuclear functions – nucleocytoplasmic transport in context

Abstract

A recent meeting of cell biologists in Cleveland, Ohio (April 22/23, 2004) highlighted the value of juxtaposing discussions of the functional organization of the nuclear periphery with themechanisms bywhich the nucleus receives signals, both from the cell surface and from defined sites in the cytoplasm. The event was jointly organized by theCell Biology Program of Case Western Reserve University School of Medicine and the Cell Biology Department and Lerner Research Institute of the Cleveland Clinic Foundation. In introductory remarks, Alan Tartakoff (Case Western Reserve University) highlighted the breadth of importance of dynamic nucleocytoplasmic communication. He described contemporary molecular understanding of TMsignaling∫ to the nucleus as one of the recent TMconquests∫ of cell biology, which characteristically insists on mechanistic questions which involve topologic or topographic issues. He also called attention to the realization that many examples of nuclear import and export do not directly involve the TMclassic∫ transport pathways which are driven by theRanGTPase andmembers of the family of importins/exportins (also known as TMkaryopherins∫) (Gˆrlich and Kutay, 1999; Xu and Massague, 2004). He further emphasized that net relocalization of proteins from the nucleus to the cytoplasm (and vice versa) can ± in many cases ± result from adjustment of the rate constants of ongoing shuttling, rather that being due to TMde novo∫ unidirectional transport (Fig. 1) (Tartakoff et al., 2000). As a prelude for subsequent lectures, he then enumerated additional circumstances which can cause individual transport cargoes to distribute asymmetrically across the nuclear envelope: unmasking of transport signals and protein-protein interaction domains (due to covalent changes or displacement of inhibitory peptide domains), tethering of cargo proteins to immobile structures (either covalently or non-covalently), etc.