Multiple sensory G proteins in the olfactory, gustatory and nociceptive neurons modulate longevity in Caenorhabditis elegans.
The life span of the nematode Caenorhabditis elegans is under control of sensory signals detected by the amphid neurons. In these neurons, C. elegans expresses at least 13 Galpha subunits and a Ggamma subunit, which are involved in the transduction and modulation of sensory signals. Here, we show that loss-of-function mutations in the Galpha subunits odr-3, gpa-1 and gpa-9, in the Ggamma subunit gpc-1 and the introduction of extra copies of the Galpha subunit gpa-11 extend the life span of C. elegans. Loss-of-function of odr-3 and extra copies of gpa-11 act synergistically and can together extend life span more than two-fold, indicating that sensory signals play an important role in regulating life span. We show that gpa-1, gpa-11, odr-3 and gpc-1 all signal via the daf-16 FOXO family transcription factor. In addition, odr-3 and gpa-11 might suppress life span extension partially independent of the insulin/IGF-1 like receptor homologue daf-2. Our results suggest that the previously unanticipated nociceptive ASH and/or ADL neurons regulate longevity. We expect that the implication of specific G proteins will eventually contribute to the identification of the sensory cues that determine the rate of aging in C. elegans.
Lans
Hannes
H
MGC Department of Cell Biology and Genetics, Center for Biomedical Genetics, Erasmus MC, 3000 CA Rotterdam, The Netherlands.
Jansen
Gert
G
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D051858:Forkhead Transcription Factors; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D017238:Genes, Helminth; D008136:Longevity / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D009475:Neurons, Afferent / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D044388:GTP-Binding Protein gamma Subunits; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; C454139:gpc-1 protein, C elegans; C110666:odr-3 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go