title: Protein Phosphatase 1 Down Regulates ZYG-1 Levels to Limit Centriole Duplication.
abstract: In humans perturbations of centriole number are associated with tumorigenesis and microcephaly, therefore appropriate regulation of centriole duplication is critical. The C. elegans homolog of Plk4, ZYG-1, is required for centriole duplication, but our understanding of how ZYG-1 levels are regulated remains incomplete. We have identified the two PP1 orthologs, GSP-1 and GSP-2, and their regulators I-2SZY-2 and SDS-22 as key regulators of ZYG-1 protein levels. We find that down-regulation of PP1 activity either directly, or by mutation of szy-2 or sds-22 can rescue the loss of centriole duplication associated with a zyg-1 hypomorphic allele. Suppression is achieved through an increase in ZYG-1 levels, and our data indicate that PP1 normally regulates ZYG-1 through a post-translational mechanism. While moderate inhibition of PP1 activity can restore centriole duplication to a zyg-1 mutant, strong inhibition of PP1 in a wild-type background leads to centriole amplification via the production of more than one daughter centriole. Our results thus define a new pathway that limits the number of daughter centrioles produced each cycle.
authors.affiliation: Department of Biology, The College of New Jersey, Ewing, NJ, United States of America.
authors.forename: Nina
authors.identifier: 0000-0002-4277-4106
authors.initials: N
authors.lastname: Peel
authors.affiliation: Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Drive, Bethesda, MD, United States of America.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Iyer
authors.affiliation: Department of Biology, The College of New Jersey, Ewing, NJ, United States of America.
authors.forename: Anar
authors.initials: A
authors.lastname: Naik
authors.affiliation: Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Drive, Bethesda, MD, United States of America.
authors.forename: Michael P
authors.identifier: 0000-0001-6609-2727
authors.initials: MP
authors.lastname: Dougherty
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Decker
authors.affiliation: Laboratory of Biochemistry and Genetics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 8 Center Drive, Bethesda, MD, United States of America.
authors.forename: Kevin F
authors.initials: KF
authors.lastname: O'Connell
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002502:Centrioles / Q000378:metabolism*; D015536:Down-Regulation; D009154:Mutation; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D054645:Protein Phosphatase 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C000619234:SDS-22 protein, C elegans; C000619235:SZY-2 protein, C elegans; D011494:Protein Kinases; C429649:zyg-1 protein, C elegans; D054645:Protein Phosphatase 1