Article ; Online: Genetic analysis of DAF-18/PTEN missense mutants for the ability to maintain quiescence of the somatic gonad and germ line in Caenorhabditis elegans dauer larvae.
2022 Volume 12, Issue 6
Abstract: The mammalian tumor suppressor PTEN has well-established lipid phosphatase and protein phosphatase activities. DAF-18, the Caenorhabditis elegans ortholog of PTEN, has a high degree of conservation in the catalytic domain, and human PTEN complements a ... ...
Abstract | The mammalian tumor suppressor PTEN has well-established lipid phosphatase and protein phosphatase activities. DAF-18, the Caenorhabditis elegans ortholog of PTEN, has a high degree of conservation in the catalytic domain, and human PTEN complements a null allele of daf-18, suggesting conserved protein function. Insights gleaned from studies of mammalian PTEN have been applied to studies of DAF-18 in C. elegans, including predicted enzymatic properties of mutants. Here, we characterize DAF-18 missense mutants previously treated as selectively disrupting either protein or lipid phosphatase activity in genetic assays to connect distinct phenotypes to specific enzymatic activities of DAF-18/PTEN. We analyze the ability of these mutants to maintain quiescence of the somatic gonad and germ line in dauer larvae, a state of diapause during which development is suspended. We show that transgenes expressing either the putative lipid phosphatase-deficient or putative protein phosphatase-deficient form fail to complement a daf-18 null allele, and that the corresponding homozygous endogenous missense mutant alleles fail to maintain developmental quiescence. We also show that the endogenous daf-18 missense alleles fail to complement each other, suggesting that one or both of the missense forms are not activity-selective. Furthermore, homozygous daf-18 missense mutants have a more severe phenotype than a daf-18 null mutant, suggesting the presence of functionally compromised mutant DAF-18 is more deleterious than the absence of DAF-18. We discuss how these genetic properties complicate the interpretation of genetic assays to associate specific enzymatic activities with specific phenotypes. |
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MeSH term(s) | Animals ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Germ Cells/metabolism ; Gonads/metabolism ; Larva ; Lipids ; Mammals ; Mutation |
Chemical Substances | Caenorhabditis elegans Proteins ; DAF-18 protein, C elegans ; Lipids |
Language | English |
Publishing date | 2022-04-21 |
Publishing country | England |
Document type | Journal Article |
ZDB-ID | 2629978-1 |
ISSN | 2160-1836 ; 2160-1836 |
ISSN (online) | 2160-1836 |
ISSN | 2160-1836 |
DOI | 10.1093/g3journal/jkac093 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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