APY-1, a novel Caenorhabditis elegans apyrase involved in unfolded protein response signalling and stress responses.
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.
Uccelletti
D
D
Department of Developmental and Cell Biology, University of Rome "La Sapienza," 00185 Rome, Italy.
Pascoli
A
A
Farina
F
F
Alberti
A
A
Mancini
P
P
Hirschberg
C B
CB
Palleschi
C
C
D000818:Animals; D030801:Animals, Genetically Modified; D001081:Apyrase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018509:DNA, Helminth / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D006031:Glycosylation; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010614:Pharynx / Q000201:enzymology / Q000254:growth & development; D017510:Protein Folding; D011755:Pyrophosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D011755:Pyrophosphatases; C023273:uridine diphosphatase; D001081:Apyrase