The transcriptional repressor CTBP-1 functions in the nervous system of <em>Caenorhabditis elegans</em> to regulate lifespan — ASN Events

The transcriptional repressor CTBP-1 functions in the nervous system of Caenorhabditis elegans to regulate lifespan (#98)

Anna Reid 1 , Duygu Yücel 2 , Mallory Wood 1 , Estelle Llamosas 1 , Sashi Kant 1 , Merlin Crossley 3 , Hannah Nicholas 1
  1. The University of Sydney, Marrickville, NSW, Australia
  2. Department of Medical Biology, Faculty of Medicine, Erciyes University, Kayseri, Melikgazi, Turkey
  3. School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW, Australia

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 re-expressing CTBP-1 in the nervous system 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, a site 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.