The function of Nup358 in nuclear protein import

• Applicant: Professor Dr. Ralph Kehlenbach
• Subject Area: Biochemistry
• Term: from 2006 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 31866324

Nucleocytoplasmic transport occurs through nuclear pore complexes (NPCs), large structures that are embedded between the inner and outer nuclear membrane. Nucleoporins (the components of the NPC) that localize asymmetrically to either the nuclear or the cytoplasmic side of the NPC have been suggested to function as initial or terminal binding sites for transport complexes. The cytoplasmic nucleoporins Nup214 and Nup358, however, were recently shown to be dispensable for transport of standard import cargoes into the nucleus. In contrast to these findings on standard cargoes, we found two proteins, whose nuclear import is strongly impaired in Nup358-deficient cells. The Rev protein of the human immunodeficiency virus and the cellular protein TERT (telomerase reverse transcriptase) are both nuclear in control cells but largely restricted to the cytoplasm in cells with reduced concentrations of Nup358. We therefore set out to analyze the effect of Nup358-depletion on proteins from a large collection of open reading frames obtained from Dr. Wiemann (DKFZ, Heidelberg). Our preliminary results suggest that about 5-10% of nuclear proteins require Nup358 for efficient nuclear import. Our goals are: a) to identify more Nup358-dependent proteins. b) to characterize the nuclear import pathways of our candidate proteins and to analyze the underlying molecular mechanisms of Nup358-dependent import. c) to analyze potential Nup214- dependent import of proteins.

• DFG Programme: Research Grants