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

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.

• Authors: D Uccelletti, A Pascoli, F Farina, A Alberti, P Mancini, C B Hirschberg, C Palleschi
• Journal: Molecular biology of the cell (Mol Biol Cell) Vol. 19 Issue 4 Pg. 1337-45 (Apr 2008) ISSN: 1939-4586 [Electronic] United States
• PMID: 18216284 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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