Functional analysis of phosphatidyliositol-bindin proteins in fission yeast

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Recent progress in the Schizosaccharomyces pombe genome project has revealed that most of genes required for the synthesis of phosphoinositides are conserved between S.pombe and Saccharomyces cerevisiae. We have cloned the gene, vps34/pik3, encoding a phosphatidylinositol (PtdIns) 3-kinase from S.pombe. In this project, we have identified and characterized PX and FYVE domain-containing proteins in S. pombe.1.Among various PX domain-containing proteins, Vps5p and Vps17p, homologues of sorting nexins, were found to be required for efficient sporulation, vacuolar protein sorting and vacuolar biogenesis in S.pombe cells.2.The FYVE-domain containing Ste12 protein catalyzes a PtdIns 3-P 5-kinase, which is required for efficient mating. Suppressor mutants for sterility of ste12 cells were identified. Of these, sst4/vps27 has been identified. The fission yeast Sst4p contain FYVE domain, and Sst4p is shown to be required for vacuolar protein and multivesicular sortings in S.pombe.3.Valproic acid (VPA) is widely used to treat epilepsy and manic-depressive illness. A genetic screen for fission yeast mutants that show hypersensitivity to VPA was isolated. One of the genes that we identified was vps45+, which encodes a member of Sec1/Munc18 family that is implicated PtdIns-dependent membrane trafficking.