title: The transcriptional repressor CTBP-1 functions in the nervous system of Caenorhabditis elegans to regulate lifespan.
abstract: C-terminal binding proteins (CtBPs) are recruited by a variety of transcription factors to mediate gene repression. Nematode CTBP-1 has previously been shown to play a role in the regulation of lifespan; Caenorhabditis elegans strains carrying a deletion in the ctbp-1 gene showed a 10-20% increase in mean and maximal lifespan compared with wild-type control strains. We set out to identify the tissues in which CTBP-1 functions to regulate lifespan in C. elegans. Our analysis of reporter genes shows that CTBP-1 is predominantly expressed in the nervous system with lower levels detectable in the hypodermis. Tissue-specific rescue experiments demonstrated that CTBP-1 functions in the nervous system to regulate lifespan. Previously, the lifespan extension in a ctbp-1 mutant was attributed, at least in part, to the misregulation of a lipase gene, lips-7. We therefore focussed on lips-7 and found that expressing CTBP-1 solely in the nervous system of a ctbp-1 mutant significantly reduced lips-7 transcription. In addition, we studied another ctbp-1 mutant allele that also displayed a long-lived phenotype. In this case, lips-7 expression was unaffected. This observation argues that, while lips-7 may play a role in lifespan, its de-repression is not essential for the extension of lifespan phenotype. We show that a prominent site of LIPS-7 expression is the hypodermis, one of the sites of fat storage in C. elegans. Interestingly, we did not observe co-localisation of CTBP-1 and lips-7 transcription in the nervous system, indicating that CTBP-1 may be acting indirectly, in a cell non-autonomous manner. In summary, our data confirm that CTBP-1 is involved in the regulation of lips-7 transcription but suggest that it may perform additional roles in the nervous system that contribute to the regulation of longevity.
authors.affiliation: School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Anna
authors.initials: A
authors.lastname: Reid
authors.affiliation: School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Duygu
authors.initials: D
authors.lastname: Yücel
authors.affiliation: School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Mallory
authors.initials: M
authors.lastname: Wood
authors.affiliation: School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Estelle
authors.initials: E
authors.lastname: Llamosas
authors.affiliation: School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Sashi
authors.initials: S
authors.lastname: Kant
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, NSW 2052, Australia.
authors.forename: Merlin
authors.initials: M
authors.lastname: Crossley
authors.affiliation: School of Molecular Bioscience, The University of Sydney, Sydney, NSW 2006, Australia. Electronic address: hannah.nicholas@sydney.edu.au.
authors.forename: Hannah
authors.initials: H
authors.lastname: Nicholas
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D017930:Genes, Reporter; D008049:Lipase / Q000235:genetics; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D009424:Nervous System Physiological Phenomena; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C525550:CTBP-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D020033:Protein Isoforms; D012097:Repressor Proteins; D008049:Lipase
keywords: Caenorhabditis elegans; CtBP; Lifespan; Lipid metabolism; Nervous system; lips-7