Transport of proteins across the nuclear envelope : the Ran GTPase system and nuclear import of heat shock proteins

Nucleocytoplasmic trafficking of macromolecules and heat shock proteins are key elements of the stress response; the analysis of nuclear transport and hsp70s will therefore contribute significantly to our understanding of cell physiology.To study the formation of the Ran/Gsp1p nucleocytoplasmic gradient, an essential component of many nuclear transport reactions, I have used mutant strains of the yeast Saccharomyces cerevisiae. My experiments have identified the nucleoporins Nup133p, Rat2p/Nup120p, Nup85p, Nic96p and the enzyme acetyl-CoA carboxylase (MTR7) as proteins that regulate the distribution and cellular concentration of Ran/Gsp1p. Moreover, I have defined the mechanisms that underlie the control of the Ran/Gsplp gradient formation by these factors.Using HeLa cells as a model system, I have demonstrated that the C-terminal part of mammalian hsc73 contains a unique targeting signal that is necessary and sufficient for stress-induced nuclear accumulation. This C-terminal segment promotes shuttling between nucleus and cytoplasm and has unique requirements for stress-dependent nuclear import