An NDPase links ADAM protease glycosylation with organ morphogenesis in C. elegans

Abstract

In the nematode Caenorhabditis elegans, the gonad acquires two U-shaped arms through the directed migration of its distal tip cells (DTCs), which are located at the tip of the growing gonad arms. A member of the ADAM (a disintegrin and metalloprotease) family, MIG-17, regulates directional migration of DTCs: MIG-17 is synthesized and secreted from the muscle cells of the body wall, and diffuses to the gonad where it is required for DTC migration. The mig-23 mutation causes defective migration of DTCs and interacts genetically with mig-17. Here, we report that mig-23 encodes a membrane-bound nucleoside diphosphatase (NDPase) required for glycosylation and proper localization of MIG-17. Our findings indicate that an NDPase affects organ morphogenesis through glycosylation of the MIG-17 ADAM protease.

ire-1-dependent Transcriptional Up-regulation of a Lumenal Uridine Diphosphatase from Caenorhabditis elegans

“…To identify nematode proteins responsible for the GDP/ UDPase activities, the C. elegans genome database was searched for homologs of S. cerevisiae Gda1p, the principal yeast GDP/UDPase. This search resulted in the identification of two C. elegans ORFs, C33H5.14 and K08H10.4, in addition to the recently reported mig-23 (17). The K08H10.4 ORF has a high similarity to S. cerevisiae and S. pombe GDA1 and to a gene product encoding a rat ER UDPase (14), ENTDP5 (Fig.…”

“…Its genome encodes at least three proteins with sequence similarity to the S. cerevisiae GA ENTDPase, Gda1p. A nucleotide diphosphatase functionally homologous to the yeast Ynd1p, encoded by the mig-23 gene, was recently described in C. elegans (17). Loss of MIG-23 function results in altered gonad morphogenesis, demonstrating the importance of this enzyme (17).…”

“…A nucleotide diphosphatase functionally homologous to the yeast Ynd1p, encoded by the mig-23 gene, was recently described in C. elegans (17). Loss of MIG-23 function results in altered gonad morphogenesis, demonstrating the importance of this enzyme (17). Here we report the presence of cation-dependent nucleotide di-and tri-phosphatase activities in membranes of C. elegans and the characterization of UDA-1 and NTP-1; the former is related, in substrate specificity, to the yeast Gda1p, whereas the latter is an apyrase and is related to the yeast Ynd1p.…”

APY-1, a NovelCaenorhabditis elegansApyrase Involved in Unfolded Protein Response Signalling and Stress Responses

“…Although protein glycosylation modulates a wide variety of intracellular events, the defect induced by the apy-1 loss-offunction has a particular effect on the pharynx development. A similar specific influence was observed with mutations of MIG-23, an NDPase that affects gonad morphogenesis through abnormal glycosylation of the MIG-17 ADAM protease (Nishiwaki et al, 2004). Thus it is possible that, beside the role in the UPR signaling, defects in apy-1 activity may affect a certain set of glycoproteins, resulting in cell type-or tissue-specific defects.…”

“…Its genome encodes at least three proteins belonging to the former family of ENTPDases with sequence similarity to the Saccharomyces cerevisiae Golgi apparatus (GA) Gda1p: UDA-1 related, in substrate specificity, to the yeast Gda1p, NTP-1 an apyrase related to the yeast Ynd1p (Abeijon et al, 1993;Xiao-Dong et al, 1999;Zhong and Guidotti, 1999;Uccelletti et al, 2004) and a nucleotide diphosphatase functionally homologous to the yeast Ynd1p, encoded by the mig-23 gene. Loss of MIG-23 function results in altered gonad morphogenesis, demonstrating the importance of this enzyme (Nishiwaki et al, 2004). Transcription of uda-1 but not ntp-1 and mig-23 was up-regulated by conditions causing ER stress and the accumulation of unfolded proteins such as tunicamycin, or high temperature; however, no relevant phenotypes were associated with loss-of-function mutation in uda-1 obtained by RNA interference (RNAi; Uccelletti et al, 2004).…”