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3.
Aging Cell ; 10(6): 1021-31, 2011 Dec.
Article in English | MEDLINE | ID: mdl-21933341

ABSTRACT

In Caenorhabditis elegans, the insulin/IGF pathway participates in the decision to initiate dauer development. Dauer is a diapause stage that is triggered by environmental stresses, such as a lack of nutrients. Insulin/IGF receptor mutants arrest constitutively in dauer, an effect that can be suppressed by mutations in other elements of the insulin/IGF pathway or by a reduction in the activity of the nuclear hormone receptor daf-12. We have isolated a pkc-1 mutant that acts as a novel suppressor of the dauer phenotypes caused by insulin/IGF receptor mutations. Interactions between insulin/IGF mutants and the pkc-1 suppressor mutant are similar to those described for daf-12 or the DAF-12 coregulator din-1. Moreover, we show that the expression of the DAF-12 target daf-9, which is normally elevated upon a reduction in insulin/IGF receptor activity, is suppressed in a pkc-1 mutant background, suggesting that pkc-1 could link the daf-12 and insulin/IGF pathways. pkc-1 has been implicated in the regulation of peptide neurosecretion in C. elegans. Although we demonstrate that pkc-1 expression in the nervous system regulates dauer formation, our results suggest that the requirement for pkc-1 in neurosecretion is independent of its role in modulating insulin/IGF signalling. pkc-1 belongs to the novel protein kinase C (nPKC) family, members of which have been implicated in insulin resistance and diabetes in mammals, suggesting a conserved role for pkc-1 in the regulation of the insulin/IGF pathway.


Subject(s)
Caenorhabditis elegans/metabolism , Gene Expression Regulation/physiology , Life Cycle Stages/genetics , Longevity/genetics , Protein Kinase C , Signal Transduction/genetics , Somatomedins/metabolism , Adaptation, Physiological , Animals , Animals, Genetically Modified , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Genotype , Humans , Insulin/metabolism , Mutation , Phenotype , Protein Kinase C/genetics , Protein Kinase C/metabolism , Receptor, Insulin/genetics , Receptor, Insulin/metabolism , Receptors, Cytoplasmic and Nuclear/genetics , Receptors, Cytoplasmic and Nuclear/metabolism , Somatomedins/genetics , Transcription Factors/genetics , Transcription Factors/metabolism
4.
Yeast ; 25(12): 879-89, 2008 Dec.
Article in English | MEDLINE | ID: mdl-19160455

ABSTRACT

In Saccharomyces yeasts, the FLO11 gene encodes an adhesin involved in filamentation, invasive growth, flocculation and adherence to solid surfaces. In wild Saccharomyces flor yeasts, a particularly expanded FLO11 allele also confers to these yeasts the ability to float under stressing liquid environments. We report here that, under optimal laboratory conditions, the repeats domain of the FLO11 gene in these wild yeasts is extremely unstable. Changes in length in the FLO11 coding repeats domain affected Flo11p-associated functions but, interestingly, some of these functions were affected more than others. Therefore, length variations in this single gene provide a combinatorial diversity, which may contribute to a very rapid adaptation to fluctuating environments. Functional analysis of contracted alleles indicated that buoyancy was not associated to FLO11 length. In contrast, this property depended on the different types of repetitive units found in this gene. Thus, not only variations in the number of intragenic repeats but also the abundance and/or distribution of the different repetitive units may have phenotypic and evolutionary implications.


Subject(s)
Membrane Proteins/genetics , Polymorphism, Genetic , Repetitive Sequences, Nucleic Acid/genetics , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/physiology , Adaptation, Physiological , Amino Acid Sequence , Evolution, Molecular , Gene Expression Regulation, Fungal , Membrane Glycoproteins , Molecular Sequence Data , Mutation , Phenotype , Recombination, Genetic , Saccharomyces/genetics , Tandem Repeat Sequences/genetics
6.
Proc Natl Acad Sci U S A ; 103(30): 11228-33, 2006 Jul 25.
Article in English | MEDLINE | ID: mdl-16844788

ABSTRACT

In nature, Saccharomyces yeasts manifest a number of adaptive responses to overcome adverse environments such as filamentation, invasive growth, flocculation and adherence to solid surfaces. Certain Saccharomyces wild yeasts, namely "flor yeasts," have also acquired the ability to form a buoyant biofilm at the broth surface. Here we report that mutations in a single gene, identified as FLO11, separate these "floating" yeasts from their nonfloating relatives. We have determined that the capability to form a self-supporting biofilm at the liquid surface is largely dependent on two changes in the FLO11 gene. First, we identified a 111-nt deletion within a repression region of the FLO11 promoter that significantly increases FLO11 gene expression. Secondly, we found rearrangements within the central tandem repeat domain of the coding region that yield a more hydrophobic Flo11p variant. Together, these mutations result in dramatic increase in cell surface hydrophobicity, which in turn confers these yeasts the ability to float by surface tension, an adaptive mechanism to gain direct access to oxygen within oxygen-poor liquid environments.


Subject(s)
Membrane Proteins/genetics , Membrane Proteins/physiology , Mutation , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/physiology , Saccharomyces/genetics , Saccharomyces/physiology , Alleles , Base Sequence , Biofilms , Cell Membrane/metabolism , Evolution, Molecular , Genetic Variation , Membrane Glycoproteins , Models, Genetic , Molecular Sequence Data , Promoter Regions, Genetic , Saccharomyces/metabolism
7.
Aging Cell ; 4(2): 87-95, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15771612

ABSTRACT

The insulin/insulin-like growth factor-1 (Ins/IGF-1) pathway regulates the aging rate of the nematode Caenorhabditis elegans. We describe other features of the three Ins/IGF-1 mutants daf-2, age-1 and aap-1. We show that the investigated Ins/IGF-1 mutants all have a reduced body volume, reduced reproductive capacity, increased ATP concentrations and an elevated stress resistance. We also observed that heat production is lower in these mutants, although the respiration rate was similar or higher compared with wild-type individuals, suggesting a metabolic shift in these mutants.


Subject(s)
Caenorhabditis elegans/physiology , Insulin-Like Growth Factor I/genetics , Insulin/genetics , Adenosine Triphosphate/metabolism , Aging/genetics , Aging/physiology , Animals , Body Size , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Heat-Shock Response , Mutation , Oxygen Consumption , Reproduction
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