RRC ID 46019
Author Kulalert W, Kim DH.
Title The unfolded protein response in a pair of sensory neurons promotes entry of C. elegans into dauer diapause.
Journal Curr Biol
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.
Volume 23(24)
Pages 2540-5
Published 2013-12-16
DOI 10.1016/j.cub.2013.10.058
PII S0960-9822(13)01333-X
PMID 24316205
PMC PMC3870035
MeSH Animals Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism Caenorhabditis elegans / physiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology Cell Cycle Proteins / metabolism Endoplasmic Reticulum Stress* Eukaryotic Initiation Factor-2 / metabolism Gene Expression Regulation, Developmental Homeostasis Insulins MAP Kinase Kinase 1 / metabolism Mutation Phosphorylation Receptor, Insulin / genetics Receptor, Insulin / physiology Sensory Receptor Cells / metabolism* Sensory Receptor Cells / physiology Unfolded Protein Response*
IF 9.601
Times Cited 14
C.elegans tm2308 tm2482 tm629