Protein phosphatase 1 down regulates ZYG-1 levels to limit centriole duplication
| Autor: | Jyoti Iyer, Anar Naik, Kevin F. O’Connell, Nina Peel, Markus Decker, Michael P. Dougherty |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cancer Research Embryology Microcephaly Centrosomes Nematoda Centriole Mutant medicine.disease_cause Biochemistry 0302 clinical medicine RNA interference Protein Phosphatase 1 Cell Cycle and Cell Division Genetics (clinical) Centrioles Genetics 0303 health sciences Mutation 030302 biochemistry & molecular biology Centriole duplication Animal Models Precipitation Techniques Cell biology Nucleic acids Genetic interference Experimental Organism Systems Cell Processes Epigenetics Cellular Structures and Organelles Research Article PLK4 lcsh:QH426-470 Down-Regulation Biology Research and Analysis Methods 03 medical and health sciences Model Organisms Gene Types medicine Animals Immunoprecipitation Caenorhabditis elegans Caenorhabditis elegans Proteins Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology Embryos Organisms Biology and Life Sciences Protein phosphatase 1 Cell Biology medicine.disease Invertebrates lcsh:Genetics 030104 developmental biology Caenorhabditis RNA Regulator Genes Gene expression Carrier Proteins Carcinogenesis Protein Kinases 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | PLoS Genetics PLoS genetics PLoS Genetics, Vol 13, Iss 1, p e1006543 (2017) |
| DOI: | 10.1101/093492 |
| Popis: | 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. Author Summary The centrosomes are responsible for organizing the mitotic spindle a microtubule-based structure that centers, then segregates, the chromosomes during cell division. When a cell divides it normally possesses two centrosomes, allowing it to build a bipolar spindle and accurately segregate the chromosomes to two daughter cells. Appropriate control of centrosome number is therefore crucial to maintaining genome stability. Centrosome number is largely controlled by their regulated duplication. In particular, the protein Plk4, which is essential for duplication, must be strictly limited as an overabundance leads to excess centrosome duplication. We have identified protein phosphatase 1 as a critical regulator of the C. elegans Plk4 homolog (known as ZYG-1). When protein phosphatase 1 is down-regulated, ZYG-1 levels increase leading to centrosome amplification. Thus our work identifies a novel mechanism that limits centrosome duplication. |
| Databáze: | OpenAIRE |
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