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Dr. Ryan
http://www.bio.tamu.edu/FACMENU/FACULTY/RyanK.htm Nuclear Pore Complexes (NPCs) span the nuclear envelope to allow for the bi-directional transport of metabolites, proteins, and RNAs between the nucleus and cytoplasm; they function to link gene expression to cellular physiology. Although the protein composition of NPCs has been defined, how these proteins assemble to form a functional complex remains unclear. The NPC's complexity and large size (~60 MDa) predicts that its assembly involves numerous discrete events, and intermediates have been observed. Using biochemical, genetic, and cell biological strategies in Saccharomyces cerevisiae, we investigate the molecular mechanisms leading to NPC biogenesis. We identify and characterize a collection of NPC assembly mutants that arrest at different points along the assembly pathway. This allows us to identify new intermediates and the factors regulating the transitions between stages. We also focus on understanding the interaction between Ran, a small GTPase, and Kap95, an importin/karyopherin, which function antagonistically in assembly. Together these two proteins spatially restrict the targeting of a subset of NPC assembly factors to the outer nuclear membrane. This targeting involves a novel, vesicular intermediate. Our research into the molecular mechanism of NPC assembly will provide insights into numerous basic cellular processes including protein trafficking, vesicle targeting, and membrane fusion. |
