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Ryan, Kathryn Instructional Associate Professor


1. Delineate the function of the Ran cycle in NPC assembly

Model for NPC AssemblyRan is a small GTPase that cycles between a GTP and GDP bound form to regulate many nuclear processes. All 4 components of the Ran cycle were isolated in the npa screen. Characterization of these mutants revealed membrane defects and the accumulation of nucleoporin containing vesicles in the cytoplasm. The accumulation of such vesicles in these npa mutants suggests that NPC assembly involves a Ran-mediated vesicular fusion event at the outer nuclear envelope. In this model of NPC assembly, a subset of nucleoporins is first concentrated in vesicles (A). When the vesicles fuse with the outer nuclear membrane in a Ran-dependent manner (B), a critical, localized concentration of these nucleoporins triggers pore formation (C) and nucleates new NPC assembly (D and E). To test the model, work is being done to characterize these vesicles. This includes biochemical approaches to purify vesicles and cell biological and genetic approaches to determine how vesicle-associated proteins contribute to NPC assembly. In addition, we are working to understand how Ran interacts with these vesicles to mediate vesicle fusion to the outer nuclear membrane.

2. Define additional steps in the NPC assembly pathway

There are events both upstream and downstream of the Ran cycle in the assembly pathway. Further cloning and characterization of mutants from the npa collection will continue to identify factors involved in other steps of NPC biogenesis and provide a platform from which to study these discrete events.

HR job title

  • Instructional Associate Professor