APY-1, a novel Caenorhabditis elegans apyrase involved in unfolded protein response signalling and stress responses

Mol Biol Cell. 2008 Apr;19(4):1337-45. doi: 10.1091/mbc.e07-06-0547. Epub 2008 Jan 23.

Abstract

Protein glycosylation modulates a wide variety of intracellular events and dysfunction of the glycosylation pathway has been reported in a variety of human pathologies. Endo-apyrases have been suggested to have critical roles in protein glycosylation and sugar metabolism. However, deciphering the physiological relevance of Endo-apyrases activity has actually proved difficult, owing to their complexity and the functional redundancy within the family. We report here that a UDP/GDPase, homologous to the human apyrase Scan-1, is present in the membranes of Caenorhabditis elegans, encoded by the ORF F08C6.6 and hereinafter-named APY-1. We showed that ER stress induced by tunicamycin or high temperature resulted in increased transcription of apy-1. This increase was not observed in C. elegans mutants defective in ire-1 or atf-6, demonstrating the requirement of both ER stress sensors for up-regulation of apy-1. Depletion of APY-1 resulted in constitutively activated unfolded protein response. Defects in the pharynx and impaired organization of thin fibers in muscle cells were observed in adult worms depleted of APY-1. Some of the apy-1(RNAi) phenotypes are suggestive of premature aging, because these animals also showed accumulation of lipofuscin and reduced lifespan that was not dependent on the functioning of DAF-2, the receptor of the insulin/IGF-1 signaling pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Apyrase / antagonists & inhibitors
  • Apyrase / genetics
  • Apyrase / metabolism*
  • Base Sequence
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans / metabolism*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • DNA, Helminth / genetics
  • Endoplasmic Reticulum / metabolism
  • Gene Expression Regulation
  • Genes, Helminth
  • Glycosylation
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Mutation
  • Pharynx / enzymology
  • Pharynx / growth & development
  • Protein Folding
  • Pyrophosphatases / antagonists & inhibitors
  • Pyrophosphatases / genetics
  • Pyrophosphatases / metabolism
  • RNA Interference
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction

Substances

  • Caenorhabditis elegans Proteins
  • DNA, Helminth
  • Recombinant Fusion Proteins
  • Green Fluorescent Proteins
  • Pyrophosphatases
  • uridine diphosphatase
  • Apyrase