Signaling Pathways and Microtubule Function

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DESCRIPTION (provided by applicant): Our long-term goal is to understand how signaling pathways in the cell control properties of microtubules. Specifically, we will concentrate on possible roles of the protein kinase C (PKC)-mediated mitogen activated protein kinase (MAPK) and the Cdc42pICdc24p pathways in controlling microtubule stability. Our working hypothesis is based on preliminary studies in which we identified two genes involved in these pathways as multicopy suppressors of mutations in the anaphase motor proteins Cin8 and Dyn1. The genes are KRE6 that was reported to suppress the lysis phenotype of pkc1, the yeast PKC homolog, and GIC1, an effector of Cdc42p. In other preliminary experiments, we found that these suppressors may act by stabilizing microtubules. Our specific aims will be (1) to identify additional suppressors related to these pathways, (2) to characterize the effect of the suppressors on microtubule function, and (3) to study the relation between microtubule function and the above pathways. For aim 1 we will continue to investigate suppressor clones that we previously isolated. In aim 2 we will study organization and function of cytoplasmic and nuclear microtubules under the effect of the suppressors. In aim 3 we will use a genetic approach to investigate the effect of mutations in, and overexpression of, genes related to the above pathways on microtubule properties. Results obtained in this project will provide new and important information in two contexts. First, they will show how conserved signaling mechanisms that regulate polarized growth and a variety of cortical events affect microtubule--dependent processes. Second, they will show how these pathways interact.