title: The unfolded protein response in a pair of sensory neurons promotes entry of C. elegans into dauer diapause.
abstract: In response to unfavorable environmental conditions such as starvation, crowding, and elevated temperature, Caenorhabditis elegans larvae enter an alternative developmental stage known as dauer, which is characterized by adaptive changes in stress resistance and metabolism. The genetic dissection of the molecular mechanisms of the C. elegans dauer developmental decision has defined evolutionarily conserved signaling pathways of organismal neuroendocrine physiology. Here, we have identified a mechanism by which a dominant mutation in a neuronal insulin gene, daf-28(sa191), causes constitutive entry into dauer diapause. We demonstrate that expression of the mutant DAF-28 insulin peptide results in endoplasmic reticulum (ER) stress in the ASI pair of chemosensory neurons. The neuronal ER stress does not compromise cellular survival but activates PEK-1, the C. elegans ortholog of the mammalian eIF2α kinase PERK, which in turn phosphorylates Ser49 of eIF2α, specifically in the ASI neuron pair, to promote entry into dauer diapause. Our data establish a novel role for ER stress and the unfolded protein response (UPR) in promoting entry into dauer diapause and suggest that, in addition to cell-autonomous activities in the maintenance of ER homeostasis, the UPR may act in a non-cell-autonomous manner to promote organismal adaptation to stress during larval development.
authors: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors: Warakorn
authors: W
authors: Kulalert
authors: Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: dhkim@mit.edu.
authors: Dennis H
authors: DH
authors: Kim
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000254:growth & development* / Q000378:metabolism / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis; D061385:Insulins; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D011972:Receptor, Insulin / Q000235:genetics / Q000502:physiology; D011984:Sensory Receptor Cells / Q000378:metabolism* / Q000502:physiology; D056811:Unfolded Protein Response
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D015852:Eukaryotic Initiation Factor-2; D061385:Insulins; C473608:daf-28 protein, C elegans; D011972:Receptor, Insulin; C499574:pek-1 protein, C elegans; D048369:MAP Kinase Kinase 1