Analysis of the specific function of mammalian paralogous alpha-importins

The (-importins are a family of proteins involved in multiple cellular processes such as nucleocytoplasmic transport, spindle formation, and nuclear membrane assembly. In vitro studies of individual (-importins suggest differences in substrate-specific nuclear import efficiency; however, specific functions of individual paralogs in vivo in higher organisms have not yet been investigated. Deletion of importin (7) in the germline of mice, one of the five importin (-paralogs described in this species, results in an early embryonic developmental disorder with embryonic arrest at the two-cell stage. The present project pursues two goals: First, to characterize in detail the developmental disorder of importin (7)-deficient embryos and to define the specific role of importin (7) in early embryonic development. In doing so, new binding partners of importin (7) will be identified. Second, to analyze the specificity of paralogous (-importins for selected interaction partners using a cell culture-based transport assay. For this purpose, cell lines will be obtained from already established knockout mice for all (-importins, and the binding and nuclear import efficiency of STAT proteins, NF-(κB, and RCC1 will be analyzed.