Characterization of Novel Importin-Beta Targets in Mitotic Spindle Assembly

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Temporal and spatial control of microtubule nucleation and organization are essential for several fundamental cellular processes, including cellular shape changes, intracellular transport, cell motility, cytoplasmic partitioning during embryonic development, and the separation of chromosomes during cell division. Most eukaryotic cells contain an elaborate macromolecular machine, the mitotic spindle, which ensures that a complete set of chromosomes is distributed to each subcell during cell division. Mitotic spindle assembly is a highly orchestrated process that is tightly regulated to avoid mistakes in chromosome segregation that could lead to developmental defects, cell death, or genomic instability. Using the Xenopus model system, the PI has identified importin-b and an interacting protein, maskin, as key proteins in the regulation of mitotic spindle assembly. This new project continues the PI's research on understanding the molecular mechanism of how importin-b and maskin regulate mitotic spindle assembly. The specific questions that will be addressed include: What is the effect on spindle assembly of altering the levels of maskin? What are the maskin interacting partner(s)? What is the effect of maskin on microtubules in vitro? Is there a link between maskin's role in spindle assembly and its role in translational regulation? How is maskin regulated? What is the role of importin-b in the regulation of maskin? Results from this project will further the understanding of the role of maskin and other mitotic spindle assembly factors in the spatial and temporal regulation of microtubule assembly and organization during early development in Xenopus, which may also shed light on the function of other members of this family of proteins. The results will also further the understanding of how importin-b regulates spindle assembly and will provide new insights into the role that importin-b and maskin and/or their human homologs play more generally in the life of a cell or an organism. The project will provide research training at three levels: undergraduate, graduate and postdoctoral.