title: C. elegans VANG-1 modulates life span via insulin/IGF-1-like signaling.
abstract: The planar cell polarity (PCP) pathway is highly conserved from Drosophila to humans and a PCP-like pathway has recently been described in the nematode Caenorhabditis elegans. The developmental function of this pathway is to coordinate the orientation of cells or structures within the plane of an epithelium or to organize cell-cell intercalation required for correct morphogenesis. Here, we describe a novel role of VANG-1, the only C. elegans ortholog of the conserved PCP component Strabismus/Van Gogh. We show that two alleles of vang-1 and depletion of the protein by RNAi cause an increase of mean life span up to 40%. Consistent with the longevity phenotype vang-1 animals also show enhanced resistance to thermal- and oxidative stress and decreased lipofuscin accumulation. In addition, vang-1 mutants show defects like reduced brood size, decreased ovulation rate and prolonged reproductive span, which are also related to gerontogenes. The germline, but not the intestine or neurons, seems to be the primary site of vang-1 function. Life span extension in vang-1 mutants depends on the insulin/IGF-1-like receptor DAF-2 and DAF-16/FoxO transcription factor. RNAi against the phase II detoxification transcription factor SKN-1/Nrf2 also reduced vang-1 life span that might be explained by gradual inhibition of insulin/IGF-1-like signaling in vang-1. This is the first time that a key player of the PCP pathway is shown to be involved in the insulin/IGF-1-like signaling dependent modulation of life span in C. elegans.
authors.affiliation: Institute of Molecular and Cellular Anatomy, Medical School, RWTH Aachen University, Aachen, Germany.
authors.forename: Sebastian J
authors.initials: SJ
authors.lastname: Honnen
authors.forename: Christian
authors.initials: C
authors.lastname: Büchter
authors.forename: Verena
authors.initials: V
authors.lastname: Schröder
authors.forename: Michael
authors.initials: M
authors.lastname: Hoffmann
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kohara
authors.forename: Andreas
authors.initials: A
authors.lastname: Kampkötter
authors.forename: Olaf
authors.initials: O
authors.lastname: Bossinger
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D016764:Cell Polarity; D051858:Forkhead Transcription Factors; D018869:Heat-Shock Response; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008136:Longevity; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D011972:Receptor, Insulin; D015398:Signal Transduction; D014157:Transcription Factors
chemical_list: D029742:Caenorhabditis elegans Proteins; D051858:Forkhead Transcription Factors; D007328:Insulin; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D014157:Transcription Factors; C549532:Vang-1 protein, C elegans; C108831:daf-16 protein, C elegans; D007334:Insulin-Like Growth Factor I; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin