title: The FEAR protein Slk19 restricts Cdc14 phosphatase to the nucleus until the end of anaphase, regulating its participation in mitotic exit in Saccharomyces cerevisiae.
abstract: In Saccharomyces cerevisiae mitosis, the protein Slk19 plays an important role in the initial release of Cdc14 phosphatase from the nucleolus to the nucleus in early anaphase, an event that is critical for proper anaphase progression. A role for Slk19 in later mitotic stages of Cdc14 regulation, however, has not been demonstrated. While investigating the role of Slk19 post-translational modification on Cdc14 regulation, we found that a triple point mutant of SLK19, slk19(3R) (three lysine-to-arginine mutations), strongly affects Cdc14 localization during late anaphase and mitotic exit. Using fluorescence live-cell microscopy, we found that, similar to slk19Δ cells, slk19(3R) cells exhibit no defect in spindle stability and only a mild defect in spindle elongation dynamics. Unlike slk19Δcells, however, slk19(3R) cells exhibit no defect in Cdc14 release from the nucleolus to the nucleus. Instead, slk19(3R) cells are defective in the timing of Cdc14 movement from the nucleus to the cytoplasm at the end of anaphase. This mutant has a novel phenotype: slk19(3R) causes premature Cdc14 movement to the cytoplasm prior to, rather than concomitant with, spindle disassembly. One consequence of this premature Cdc14 movement is the inappropriate activation of the mitotic exit network, made evident by the fact that slk19(3R) partially rescues a mutant of the mitotic exit network kinase Cdc15. In conclusion, in addition to its role in regulating Cdc14 release from the nucleolus to the nucleus, we found that Slk19 is also important for regulating Cdc14 movement from the nucleus to the cytoplasm at the end of anaphase.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California, United States of America.
authors.forename: Ann Marie E
authors.initials: AM
authors.lastname: Faust
authors.forename: Catherine C L
authors.initials: CC
authors.lastname: Wong
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: David G
authors.initials: DG
authors.lastname: Drubin
authors.forename: Georjana
authors.initials: G
authors.lastname: Barnes
mesh_terms: D000705:Anaphase; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002466:Cell Nucleolus / Q000378:metabolism*; D015870:Gene Expression; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D021381:Protein Transport; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: C074860:CDC14 protein, S cerevisiae; D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; C437104:Slk19 protein, S cerevisiae; D017027:Protein Tyrosine Phosphatases
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