The C. elegans lethal gut-obstructed gob-1 gene is trehalose-6-phosphate phosphatase. Export

@article{citeulike:3322870, abstract = {We identified the gob-1 (gut-obstructed) gene in a forward genetic screen for intestinal defects in the nematode Caenorhabditis elegans. gob-1 loss of function results in early larval lethality, at least in part because of a blocked intestinal lumen and consequent starvation. The gob-1 gene is first expressed in the 8E cell stage of the embryonic intestine, and the GATA factor ELT-2 is sufficient but not necessary for this early phase of gob-1 expression; gob-1 expression later becomes widespread in embryos, larvae, and adults. GOB-1 is a member of the HAD-like hydrolase superfamily and shows a robust and specific phosphatase activity for the substrate trehalose-6-phosphate. Trehalose is a glucose disaccharide found in bacteria, fungi, plants, insects, and nematodes but not in mammals. Trehalose plays a number of critical roles such as providing flexible energy reserves and contributing to thermal and osmotic stress resistance. In budding yeast and in plants, the intermediate in trehalose synthesis, trehalose-6-phosphate, has additional critical but less well-defined roles in controlling glycolysis and carbohydrate metabolism. Strong loss-of-function mutants in the C. elegans tps-1 and tps-2 genes (which encode the two trehalose phosphate synthases responsible for trehalose-6-phosphate synthesis) completely suppress the lethality associated with gob-1 loss of function. The suppression of gob-1 lethality by ablation of TPS-1 and TPS-2, the upstream enzymes in the trehalose synthesis pathway, suggests that gob-1 lethality results from a toxic build-up of the intermediate trehalose-6-phosphate, not from an absence of trehalose. GOB-1 is the first trehalose-6-phosphate phosphatase to be identified in nematodes and, because of its associated lethality and distinctive sequence properties, provides a new and attractive target for anti-parasitic drugs.}, author = {Kormish, J. D. and Mcghee, J. D.}, citeulike-article-id = {3322870}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/16197937}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=16197937}, citeulike-linkout-2 = {http://www.wormbase.org/db/misc/paper?name=WBPaper00026837}, journal = {Dev Biol}, keywords = {c33d31, c\_elegans, caenorhabditis\_elegans, celegans, elegans, elt-1, elt-2, f19h81, gob-1, h13n063, nematode, other, tps-1, tps-2, w09c21, wormbase, zk542}, pages = {35--47}, posted-at = {2008-09-23 18:29:29}, priority = {3}, title = {The C. elegans lethal gut-obstructed gob-1 gene is trehalose-6-phosphate phosphatase.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/16197937}, volume = {287}, year = {2005} }

TY - JOUR ID - citeulike:3322870 L3 - citeulike-article-id:3322870 N2 - We identified the gob-1 (gut-obstructed) gene in a forward genetic screen for intestinal defects in the nematode Caenorhabditis elegans. gob-1 loss of function results in early larval lethality, at least in part because of a blocked intestinal lumen and consequent starvation. The gob-1 gene is first expressed in the 8E cell stage of the embryonic intestine, and the GATA factor ELT-2 is sufficient but not necessary for this early phase of gob-1 expression; gob-1 expression later becomes widespread in embryos, larvae, and adults. GOB-1 is a member of the HAD-like hydrolase superfamily and shows a robust and specific phosphatase activity for the substrate trehalose-6-phosphate. Trehalose is a glucose disaccharide found in bacteria, fungi, plants, insects, and nematodes but not in mammals. Trehalose plays a number of critical roles such as providing flexible energy reserves and contributing to thermal and osmotic stress resistance. In budding yeast and in plants, the intermediate in trehalose synthesis, trehalose-6-phosphate, has additional critical but less well-defined roles in controlling glycolysis and carbohydrate metabolism. Strong loss-of-function mutants in the C. elegans tps-1 and tps-2 genes (which encode the two trehalose phosphate synthases responsible for trehalose-6-phosphate synthesis) completely suppress the lethality associated with gob-1 loss of function. The suppression of gob-1 lethality by ablation of TPS-1 and TPS-2, the upstream enzymes in the trehalose synthesis pathway, suggests that gob-1 lethality results from a toxic build-up of the intermediate trehalose-6-phosphate, not from an absence of trehalose. GOB-1 is the first trehalose-6-phosphate phosphatase to be identified in nematodes and, because of its associated lethality and distinctive sequence properties, provides a new and attractive target for anti-parasitic drugs. JF - Dev Biol EP - 47 TI - The C. elegans lethal gut-obstructed gob-1 gene is trehalose-6-phosphate phosphatase. VL - 287 SP - 35 KW - c33d31 KW - c_elegans KW - caenorhabditis_elegans KW - celegans KW - elegans KW - elt-1 KW - elt-2 KW - f19h81 KW - gob-1 KW - h13n063 KW - nematode KW - other KW - tps-1 KW - tps-2 KW - w09c21 KW - wormbase KW - zk542 AU - Kormish, JD AU - Mcghee, JD PY - 2005/// UR - http://view.ncbi.nlm.nih.gov/pubmed/16197937 ER -