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Kormish JD , McGhee JD
The C. elegans lethal gut-obstructed gob-1 gene is trehalose-6-phosphate phosphatase
Developmental Biology. 2005 ;287(1) :35-47
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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. © 2005 Elsevier Inc. All rights reserved.
Notes
00121606 (ISSN) Cited By: 0; Export Date: 25 May 2006; Source: Scopus CODEN: DEBIA; DOI: 10.1016/j.ydbio.2005.08.027 Language of Original Document: English Correspondence Address: McGhee, J.D.; Department of Biochemistry and Molecular Biology; University of Calgary Faculty of Medicine; Health Sciences Centre; 3330 Hospital Drive, N.W. Calgary, Alta. T2N 4N1, Canada; email: jmcghee@ucalgary.ca References: Altschul, S.F., Gish, W., Miller, W., Myers, E.W., Lipman, D.J., Basic local alignment search tool (1990) J. Mol. Biol., 215, pp. 403-410; Altschul, S.F., Madden, T.L., Schaffer, A.A., Zhang, J., Zhang, Z., Miller, W., Lipman, D.J., Gapped BLAST and PSI-BLAST: A new generation of protein database search programs (1997) Nucleic Acids Res., 25, pp. 3389-3402; An, J.H., Blackwell, T.K., SKN-1 links C. elegans mesendodermal specification to a conserved oxidative stress response (2003) Genes Dev., 17, pp. 1882-1893; Aravind, L., Galperin, M.Y., Koonin, E.V., The catalytic domain of the P-type ATPase has the haloacid dehalogenase fold (1998) Trends Biochem. Sci., 23, pp. 127-129; Ausubel, R.M., Brent, R., Kingston, R.E., Moore, D.D., Seidman, J.G., Smith, J.A., Struhl, K., (1994) Current Protocols in Molecular Biology, John Wiley and Sons; Baugh, L.R., Hill, A.A., Slonim, D.K., Brown, E.L., Hunter, C.P., Composition and dynamics of the Caenorhabditis elegans early embryonic transcriptome (2003) Development, 130, pp. 889-900; Baugh, L.R., Hill, A.A., Claggett, J.M., Hill-Harfe, K., Wen, J.C., Slonim, D.K., Brown, E.L., Hunter, C.P., The homeodomain protein PAL-1 specifies a lineage-specific regulatory network in the C. elegans embryo (2005) Development, 132, pp. 1843-5184; Behm, C.A., The role of trehalose in the physiology of nematodes (1997) Int. J. Parasitol., 27, pp. 215-229; Blazquez, M.A., Gancedo, C., Identification of extragenic suppressors of the cif1 mutation in Saccharomyces cerevisiae (1994) Curr. Genet., 25, pp. 89-94; Blazquez, M.A., Lagunas, R., Gancedo, C., Gancedo, J.M., Trehalose-6-phosphate, a new regulator of yeast glycolysis that inhibits hexokinases (1993) FEBS Lett., 329, pp. 51-54; Bonini, B.M., Van Dijck, P., Thevelein, J.M., Uncoupling of the glucose growth defect and the deregulation of glycolysis in Saccharomyces cerevisiae Tps1 mutants expressing trehalose-6-phosphate-insensitive hexokinase from Schizosaccharomyces pombe (2003) Biochim. Biophys. Acta, 1606, pp. 83-93; Borgonie, G., Van Driessche, E., Link, C.D., De Waele, D., Coomans, A., Tissue treatment for whole mount internal lectin staining in the nematodes Caenorhabditis elegans, Panagrolaimus superbus and Acrobeloides maximus (1994) Histochemistry, 101, pp. 379-384; Bossinger, O., Fukushige, T., Claeys, M., Borgonie, G., McGhee, J.D., The apical disposition of the Caenorhabditis elegans intestinal terminal web is maintained by LET-413 (2004) Dev. Biol., 268, pp. 448-456; Bowerman, B., Eaton, B.A., Priess, J.R., Skn-1, a maternally expressed gene required to specify the fate of ventral blastomeres in the early C. elegans embryo (1992) Cell, 68, pp. 1061-1075; Bowerman, B., Draper, B.W., Mello, C.C., Priess, J.R., The maternal gene skn-1 encodes a protein that is distributed unequally in early C. elegans embryos (1993) Cell, 74, pp. 443-452; Brenner, S., The genetics of Caenorhabditis elegans (1974) Genetics, 77, pp. 71-94; Broitman-Maduro, G., Maduro, M.F., Rothman, J.H., The noncanonical binding site of the MED-1 GATA factor defines differentially regulated target genes in the C. elegans mesendoderm (2005) Dev. Cell, 8, pp. 427-433; Chen, Q., Haddad, G.G., Role of trehalose phosphate synthase and trehalose during hypoxia: From flies to mammals (2004) J. Exp. Biol., 207, pp. 3125-3129; Chen, Q., Ma, E., Behar, K.L., Xu, T., Haddad, G.G., Role of trehalose phosphate synthase in anoxia tolerance and development in Drosophila melanogaster (2002) J. Biol. Chem., 277, pp. 3274-3279; Cogan, E.B., Birrell, G.B., Griffith, O.H., A robotics-based automated assay for inorganic and organic phosphates (1999) Anal. Biochem., 271, pp. 29-35; Collet, J.F., Stroobant, V., Pirard, M., Delpierre, G., Van Schaftingen, E., A new class of phosphotransferases phosphorylated on an aspartate residue in an amino-terminal DXDX(T/V) motif (1998) J. Biol. Chem., 273, pp. 14107-14112; Collet, J.F., Stroobant, V., Van Schaftingen, E., Mechanistic studies of phosphoserine phosphatase, an enzyme related to P-type ATPases (1999) J. Biol. Chem., 274, pp. 33985-33990; Eastmond, P.J., Graham, I.A., Trehalose metabolism: A regulatory role for trehalose-6-phosphate? (2003) Curr. Opin. Plant Biol., 6, pp. 231-235; Eastmond, P.J., Li, Y., Graham, I.A., Is trehalose-6-phosphate a regulator of sugar metabolism in plants? (2003) J. Exp. Bot., 54, pp. 533-537; Edgar, L.G., McGhee, J.D., Embryonic expression of a gut-specific esterase in Caenorhabditis elegans (1986) Dev. Biol., 114, pp. 109-118; Elbein, A.D., Pan, Y.T., Pastuszak, I., Carroll, D., New insights on trehalose: A multifunctional molecule (2003) Glycobiology, 13, pp. 17R-27R; Elliott, B., Haltiwanger, R.S., Futcher, B., Synergy between trehalose and Hsp104 for thermotolerance in Saccharomyces cerevisiae (1996) Genetics, 144, pp. 923-933; Fairbairn, D., The biochemistry of Ascaris (1957) Exp. Parasitol., 6, pp. 491-554; Fire, A., Histochemical techniques for locating Escherichia coli beta-galactosidase activity in transgenic organisms (1992) Genet. Anal., Tech. Appl., 9, pp. 151-158; Fire, A., Harrison, S.W., Dixon, D., A modular set of lacZ fusion vectors for studying gene expression in Caenorhabditis elegans (1990) Gene, 93, pp. 189-198; Francois, J., Parrou, J.L., Reserve carbohydrates metabolism in the yeast Saccharomyces cerevisiae (2001) FEMS Microbiol. Rev., 25, pp. 125-145; Fukushige, T., Hawkins, M.G., McGhee, J.D., The GATA-factor elt-2 is essential for formation of the Caenorhabditis elegans intestine (1998) Dev. Biol., 198, pp. 286-302; Fukushige, T., Hendzel, M.J., Bazett-Jones, D.P., McGhee, J.D., Direct visualization of the elt-2 gut-specific GATA factor binding to a target promoter inside the living Caenorhabditis elegans embryo (1999) Proc. Natl. Acad. Sci. U. S. A., 96, pp. 11883-11888; Fukushige, T., Goszczynski, B., Tian, H., McGhee, J.D., The evolutionary duplication and probable demise of an endodermal GATA factor in Caenorhabditis elegans (2003) Genetics, 165, pp. 575-588; Fukushige, T., Goszczynski, B., Yan, J., McGhee, J.D., Transcriptional control and patterning of the pho-1 gene, an essential acid phosphatase expressed in the C. elegans intestine (2005) Dev. Biol., 279, pp. 446-461; Gancedo, C., Flores, C.L., The importance of a functional trehalose biosynthetic pathway for the life of yeasts and fungi (2004) FEMS Yeast Res., 4, pp. 351-359; Gilleard, J.S., McGhee, J.D., Activation of hypodermal differentiation in the Caenorhabditis elegans embryo by GATA transcription factors ELT-1 and ELT-3 (2001) Mol. Cell. Biol., 21, pp. 2533-2544; Goszczynski, B., McGhee, J.D., Re-evaluation of the role of the med-1 and med-2 genes in specifying the C. elegans endoderm Genetics, in press. (Electronic publication July 5, 2005; DOI:10.1534/genetics.105. 044909).; Goyal, K., Browne, J.A., Burnell, A.M., Tunnacliffe, A., Dehydration-induced tps gene transcripts from an anhydrobiotic nematode contain novel spliced leaders and encode atypical GT-20 family proteins (2005) Biochimie, 87, pp. 565-574; Hawkins, M.G., McGhee, J.D., Elt-2, a second Gata factor from the nematode Caenorhabditis elegans (1995) J. Biol. Chem., 270, pp. 14666-14671; Hedgecock, E.M., White, J.G., Polyploid tissues in the nematode Caenorhabditis elegans (1985) Dev. Biol., 107, pp. 128-133; Hermann, G.J., Leung, B., Priess, J.R., Left-right asymmetry in C. elegans intestine organogenesis involves a LIN-12/Notch signaling pathway (2000) Development, 127, pp. 3429-3440; Koonin, E.V., Tatusov, R.L., Computer analysis of bacterial haloacid dehalogenases defines a large superfamily of hydrolases with diverse specificity. Application of an iterative approach to database search (1994) J. Mol. Biol., 244, pp. 125-132; Koppen, M., Simske, J.S., Sims, P.A., Firestein, B.L., Hall, D.H., Radice, A.D., Rongo, C., Hardin, J.D., Cooperative regulation of AJM-1 controls junctional integrity in Caenorhabditis elegans epithelia (2001) Nat. Cell Biol., 3, pp. 983-991; Lamitina, S.T., Strange, K., Transcriptional targets of DAF-16 insulin signaling pathway protect C. elegans from extreme hypertonic stress (2005) Am. J. Physiol.: Cell Physiol., 288, pp. 467-C474; Leung, B., Hermann, G.J., Priess, J.R., Organogenesis of the Caenorhabditis elegans intestine (1999) Dev. Biol., 216, pp. 114-134; Leyman, B., Van Dijck, P., Thevelein, J.M., An unexpected plethora of trehalose biosynthesis genes in Arabidopsis thaliana (2001) Trends Plant Sci., 6, pp. 510-513; Maduro, M.F., Rothman, J.H., Making worm guts: The gene regulatory network of the Caenorhabditis elegans endoderm (2002) Dev. Biol., 246, pp. 68-85; Maduro, M.F., Meneghini, M.D., Bowerman, B., Broitman-Maduro, G., Rothman, J.H., Restriction of mesendoderm to a single blastomere by the combined action of SKN-1 and a GSK-3beta homolog is mediated by MED-1 and -2 in C. elegans (2001) Mol. Cell, 7, pp. 475-485; Mello, C.C., Kramer, J.M., Stinchcomb, D., Ambros, V., Efficient gene transfer in C. elegans: Extrachromosomal maintenance and integration of transforming sequences (1991) EMBO J., 10, pp. 3959-3970; Moilanen, L.H., Fukushige, T., Freedman, J.H., Regulation of metallothionein gene transcription. Identification of upstream regulatory elements and transcription factors responsible for cell-specific expression of the metallothionein genes from Caenorhabditis elegans (1999) J. Biol. Chem., 274, pp. 29655-29665; Notredame, C., Higgins, D.G., Heringa, J., T-Coffee: A novel method for fast and accurate multiple sequence alignment (2000) J. Mol. Biol., 302, pp. 205-217; Oke, J.M., Watt, R.A., Trehalose-6-phosphate-potent anti-onchocerciatic agent (1998) Afr. J. Med. Med. Sci., 27, pp. 225-228; Page, B.D., Zhang, W., Steward, K., Blumenthal, T., Priess, J.R., ELT-1, a GATA-like transcription factor, is required for epidermal cell fates in Caenorhabditis elegans embryos (1997) Genes Dev., 11, pp. 1651-1661; Pellerone, F.I., Archer, S.K., Behm, C.A., Grant, W.N., Lacey, M.J., Somerville, A.C., Trehalose metabolism genes in Caenorhabditis elegans and filarial nematodes (2003) Int. J. Parasitol., 33, pp. 1195-1206; Piper, P.W., Lockheart, A., A temperature-sensitive mutant of Saccharomyces cerevisiae defect in the specific phosphatase of trehalose biosynthesis (1988) FEMS Microbiol. Lett., 49, pp. 245-250; Reboul, J., Vaglio, P., Tzellas, N., Thierry-Mieg, N., Moore, T., Jackson, C., Shin-I, T., (...), Vidal, M., Open-reading-frame sequence tags (OSTs) support the existence of at least 17,300 genes in C. elegans (2001) Nat. Genet., 27, pp. 332-336; Ridder, I.S., Dijkstra, B.W., Identification of the Mg2+-binding site in the P-type ATPase and phosphatase members of the HAD (haloacid dehalogenase) superfamily by structural similarity to the response regulator protein CheY (1999) Biochem. J., 339, pp. 223-226; Schluepmann, H., Pellny, T., Van Dijken, A., Smeekens, S., Paul, M., Trehalose 6-phosphate is indispensable for carbohydrate utilization and growth in Arabidopsis thaliana (2003) Proc. Natl. Acad. Sci. U. S. A., 100, pp. 6849-6854; Schluepmann, H., Van Dijken, A., Aghdasi, M., Wobbes, B., Paul, M., Smeekens, S., Trehalose mediated growth inhibition of Arabidopsis seedlings is due to trehalose-6-phosphate accumulation (2004) Plant Physiol., 135, pp. 879-890; Sulston, J.E., Schierenberg, E., White, J.G., Thomson, J.N., The embryonic cell lineage of the nematode Caenorhabditis elegans (1983) Dev. Biol., 100, pp. 64-119; Wicks, S.R., Yeh, R.T., Gish, W.R., Waterston, R.H., Plasterk, R.H., Rapid gene mapping in Caenorhabditis elegans using a high density polymorphism map (2001) Nat. Genet., 28, pp. 160-164; Yeo, M., Lin, P.S., Dahmus, M.E., Gill, G.N., A novel RNA polymerase II C-terminal domain phosphatase that preferentially dephosphorylates serine 5 (2003) J. Biol. Chem., 278, pp. 26078-26085; Zhu, J., Hill, R.J., Heid, P.J., Fukuyama, M., Sugimoto, A., Priess, J.R., Rothman, J.H., End-1 encodes an apparent GATA factor that specifies the endoderm precursor in Caenorhabditis elegans embryos (1997) Genes Dev., 11, pp. 2883-2896; Zhu, J., Fukushige, T., McGhee, J.D., Rothman, J.H., Reprogramming of early embryonic blastomeres into endodermal progenitors by a Caenorhabditis elegans GATA factor (1998) Genes Dev., 12, pp. 3809-3814.