The Nuclear Pore Complex: Interphase and Mitotic Function

University Of Utah, Salt Lake City UT

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Abstract

DESCRIPTION (provided by applicant): The nuclear compartment of eukaryotic cells provides a critical specialized microenvironment and allows for spatial and temporal control over important cellular processes. Selective flow of molecules between the nucleus and cytoplasm underlies this subcellular division and takes place exclusively through macromolecular structures termed nuclear pore complexes. Remodeling of many architectural features of the cell is a prerequisite for cell division. Both the nuclear pore complex and the membranes that enclose the nucleus are disassembled as the cell enters mitosis, in concert with chromosomal condensation and microtubule rearrangements. Indeed, components of the nuclear pore play critical roles in orchestrating remodeling events. The pore protein Nup153 will be used as an inroad into understanding how the pore contributes mechanistically to both intracellular trafficking and cell division. Specifically, in Aim 1, 2 key features of Nup153, RNA binding and transcription-dependent mobility, will be analyzed in order to better understand the interface and mechanistic links between RNA cargo and the pore complex. The second Aim focuses on the role of partner proteins of the zinc finger module found in Nup153 and Nup358 with respect to mitotic recruitment of COPI membrane remodeling machinery. In the third Aim, the connection between this zinc finger module and COPI will be targeted for disruption in order to decipher how it is integrated into the cell cycle of somatic cells. Finally, characterization of other players in the nuclear membrane remodeling machinery will be launched in the fourth Aim by examining both prime candidate proteins as well as proteins identified through analysis of interaction networks. These studies will elucidate fundamental aspects of gene expression at interphase and accurate division at mitosis. The information gathered will impact practical applications, such as optimizing expression of exogenously introduced genes as well as understanding -and ultimately controlling-growth deregulation found in cancerous cells.