title: ire-1-dependent transcriptional up-regulation of a lumenal uridine diphosphatase from Caenorhabditis elegans.
abstract: Lumenal ecto-nucleoside tri- and di-phosphohydrolases (ENTPDases) of the secretory pathway of eukaryotes hydrolyze nucleoside diphosphates resulting from glycosyltransferase-mediated reactions, yielding nucleoside monophosphates. The latter are weaker inhibitors of glycosyltransferases than the former and are also antiporters for the transport of nucleotide sugars from the cytosol to the endoplasmic reticulum (ER) and Golgi apparatus (GA) lumen. Here we describe the presence of two cation-dependent nucleotide phosphohydrolase activities in membranes of Caenorhabditis elegans: one, UDA-1, is a UDP/GDPase encoded by the gene uda-1, whereas the other is an apyrase encoded by the gene ntp-1. UDA-1 shares significant amino acid sequence similarity to yeast GA Gda1p and mammalian UDP/GDPases and has a lumenal active site in vesicles displaying an intermediate density between those of the ER and GA when expressed in S. cerevisiae. NTP-1 expressed in COS-7 cells appeared to localize to the GA. The transcript of uda-1 but not those of two other C. elegans ENTPDase mRNAs (ntp-1 and mig-23) was induced up to 3.5-fold by high temperature, tunicamycin, and ethanol. The same effectors triggered the unfolded protein response as shown by the induction of expression of green fluorescent protein under the control of the BiP chaperone promoter and the UDP-glucose:glycoprotein glucosyltransferase. Up-regulation of uda-1 did not occur in ire-1-deficient mutants, demonstrating the role of this ER stress sensor in this event. We hypothesize that up-regulation of uda-1 favors hydrolysis of the glucosyltransferase inhibitory product UDP to UMP, and that the latter product then exits the lumen of the ER or pre-GA compartment in a coupled exchange with the entry of UDP-glucose, thereby further relieving ER stress by favoring protein re-glycosylation.
authors.affiliation: Department of Molecular and Cell Biology, Boston University Goldman School of Dental Medicine, Boston, Massachusetts 02118, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Uccelletti
authors.forename: Cornelia
authors.initials: C
authors.lastname: O'Callaghan
authors.forename: Patricia
authors.initials: P
authors.lastname: Berninsone
authors.forename: Irina
authors.initials: I
authors.lastname: Zemtseva
authors.forename: Claudia
authors.initials: C
authors.lastname: Abeijon
authors.forename: Carlos B
authors.initials: CB
authors.lastname: Hirschberg
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D019556:COS Cells; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D002688:Chitinases / Q000378:metabolism; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D008969:Molecular Sequence Data; D009708:Nucleotidases / Q000378:metabolism; D010802:Phylogeny; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011755:Pyrophosphatases / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D016415:Sequence Alignment; D013312:Stress, Physiological / Q000378:metabolism; D013379:Substrate Specificity; D013696:Temperature; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D000596:Amino Acids; D011494:Protein Kinases; D009708:Nucleotidases; D002688:Chitinases; D000251:Adenosine Triphosphatases; D011755:Pyrophosphatases; C023273:uridine diphosphatase; D002118:Calcium