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Genetic, molecular and developmental analysis of the glutamine synthetase isozymes ofDrosophila melanogaster

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Abstract

The glutamine synthetase isozymes ofDrosophila melanogaster offer an attractive model for the study of the molecular genetics and evolution of a small gene family encoding enzymatic isoforms that evolved to assume a variety of specific and sometimes essential biological functions. InDrosophila melanogaster two GS. isozymes have been described which exhibit different cellular localisation and are coded by a two-member gene family. The mitochondrial GS structural gene resides at the 21B region of the second chromosome, the structural gene for the cytosolic isoform at the 10B region of the X chromosome. cDNA clones corresponding to the two genes have been isolated and sequenced. Evolutionary analysis data are in accord with the hypothesis that the twoDrosophila glutamine synthetase genes are derived from a duplication event that occurred near the time of divergence between Insecta and Vertebrata. Both isoforms catalyse all reactions catalysed by other glutamine synthetases, but the different kinetic parameters and the different cellular compartmentalisation suggest strong functional specialisation. In fact, mutations of the mitochondrial GS gene produce embryo-lethal female sterility, defining a function of the gene product essential for the early stages of embryonic development. Preliminary results show strikingly distinct spatial and temporal patterns of expression of the two isoforms at later stages of development.

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References

  • Anderson P.M. & C.A. Casey, 1984. Glutamine-dependent synthesis of citrulline by isolated hepatic mitochondria fromSqualus achantus. J. Biol. Chem. 259: 456–462.

    PubMed  Google Scholar 

  • Barsanti, P., C. Caggese, R. Marzella, C. Rutigliano & A. Zonno, 1992. Resistance to methionine sulfoximine, an inhibitor of glutamine synthetase, inDrosophila melanogaster. Atti Ass. Genet. Ital. 38: 57–58.

    Google Scholar 

  • Barsanti, P., C. Caggese, C. Saracino & G. Testini, 1993. A major genetic determinant of sensitivity to methionine sulfoximine resides in region 20A2-4 of the X chromosome ofDrosophila melanogaster. Atti Ass. Genet. Ital. 39: 49–50.

    Google Scholar 

  • Caggese, C., R. Caizzi, M.P. Bozzetti, P. Barsanti & F. Ritossa, 1988. Genetic determinants of glutamine synthetase inDrosophila melanogaster: a gene for glutamine synthetase I resides in the 21B3-6 region. Biochem. Genet. 26: 571–583.

    PubMed  Google Scholar 

  • Caggese, C., R. Caizzi, F. Grieco, M.P. Bozzetti & F. Ritossa, 1986. Genetic determinants of glutamine synthetase inDrosophila melanogaster: role of the 10B8-11 region. Mol. Gen. Genet. 204: 208–213.

    Google Scholar 

  • Caggese, C., R. Caizzi, P. Barsanti & M.P. Bozzetti, 1992. Mutations in the glutamine synthetase I (gsI) gene produce embryo-lethal female sterility inDrosophila melanogaster. Develop. Genet. 13: 359–366.

    Google Scholar 

  • Caizzi, R., M.P. Bozzetti, C. Caggese & F. Ritossa, 1990. Homologous nuclear genes encode cytoplasmic and mitochondrial glutamine synthetase inDrosophila melanogaster. J. Mol. Biol. 212: 17–26.

    PubMed  Google Scholar 

  • Caizzi, R. & F. Rotossa, 1983. The enzyme glutamine synthetase I ofDrosophila melanogaster is associated with a modified RNA. Biochem. Genet. 21: 267–285.

    PubMed  Google Scholar 

  • De Pinto, V., C. Caggese, G. Prezioso & F. Ritossa, 1987. Purification of the glutamine synthetase II isozyme ofDrosophila melanogaster and structural and functional comparison of glutamine synthetase I and II. Biochem. Genet. 25: 821–836.

    PubMed  Google Scholar 

  • Garrell, J. & J. Modolell, 1990. TheDrosophila extramacrochetae locus, an antagonist of proneural genes that, like these genes, encodes a helix-loop-helix protein. Cell 61: 39–46.

    PubMed  Google Scholar 

  • Gibbs, C.S., K.E. Campbell & R.H. Wilson, 1987. Sequence of a human glutamine synthetase cDNA. Nucl. Acids Res. 15: 6293.

    PubMed  Google Scholar 

  • Hayward, B.E., A. Hussain, R.H. Wilson, A. Lyons, B. Woodchuck, B. McIntosh & T.J.R. Harris, 1986. The cloning and nucleotide sequence of the cDNA for an amplified glutamine synthetase gene from the Chinese hamster. Nucl. Acids Res. 14: 999–1008.

    PubMed  Google Scholar 

  • Kumada, Y., D. Benson, D. Hillemann, T. Hosted, D. Rochefort, C. Thompson, W. Wohlleben & Y. Tateno, 1993. Evolution of the glutamine synthetase gene, one of the oldest existing and functioning genes. Proc. Natl. Acad. Sci. USA 90: 3009–3013.

    PubMed  Google Scholar 

  • Kuo, C.F., K.E. Paulson & J.E. Darnell, Jr., 1988. Positional and developmental regulation of glutamine synthetase expression in mouse liver. Mol. Cell. Biol. 18: 4966–4971.

    Google Scholar 

  • Lindsley, D.L. & G. Zimm, 1992. The genome ofDrosophila melanogaster. Academic Press, San Diego.

    Google Scholar 

  • Magnuson, S.R. & A.P. Young, 12988. Murine glutamine synthetase: cloning, developmental regulation, and glucocorticoid inducibility. Develop. Biol. 130: 536–542.

  • Meister, A., 1980. Catalytic Mechanism of Glutamine Synthetase; Overview of Glutamine Metabolism, pp. 1–40 in Glutamine: Metabolism, Enzymology, and Regulation, edited by J. Mora and R. Palacios. Academic Press, New York/London.

    Google Scholar 

  • Minehart, P. & B. Magasanik, 1992. Sequence of theGLN1 gene ofSaccharomyces cerevisiae: role of the upstream region in regulation of glutamine synthetase expression. J. Bacteriol. 174: 1828–1836.

    PubMed  Google Scholar 

  • Parkhurst, S.M. & V.G. Corces, 1987. Developmental expression ofDrosophila melanogaster retrovirus-like transposable element. EMBO J. 6: 419–424.

    PubMed  Google Scholar 

  • Pesole, G., M.P. Bozzetti, C. Lanave, G. Preparata & C. Saccone, 1991. Glutamine synthetase gene evolution: A good molecular clock. Proc. Natl. Acad. Sci. USA 88: 520–526.

    Google Scholar 

  • Sanders, M.M. & C. Kon, 1991. Glutamine is a powerful effector of heat shock protein expression inDrosophila Kc cells. J. Cell. Physiol. 146: 180–190.

    PubMed  Google Scholar 

  • Sanders, M.M. & C. Kon, 1992. Glutamine and glutamate metabolism in normal and heat shock conditions inDrosophila Kc cells: conditions supporting glutamine synthesis maximise heat shock polypeptide expression. J. Cell. Physiol. 150: 620–31.

    PubMed  Google Scholar 

  • Sanders, P.D. & R.H. Wilson, 1984. Amplification and cloning of the Chinese hamster glutamine synthetase gene. EMBO J. 3: 65–71.

    PubMed  Google Scholar 

  • Scalenghe, F. & F. Ritossa, 1976. Controllo della attivita genica inDrosophila: Il puff al locus ebony e la glutamina sintetasi. Atti Acc. Naz. Lincei 13: 441–528.

    Google Scholar 

  • Shankar, R.A. & P.M. Anderson, 1985. Purification and properties of glutamine synthetase from liver ofSqualus achantus. Arch. Biochem. Biophys. 239: 248–259.

    PubMed  Google Scholar 

  • Shatters, R.G. & M.L. Khan, 1989. Glutamine synthetase II inRhizobium: Reexamination of the proposed horizontal transfer of DNA from eukaryotes to prokaryotes. J. Mol. Evol. 29: 422–428.

    PubMed  Google Scholar 

  • Smith, D.J. & J. Campbell, 1983. Subcellular location of chicken brain glutamine synthetase and comparison with chicken liver mitochondrial glutamine synthetase. J. Biol. Chem. 258: 12265–12268.

    PubMed  Google Scholar 

  • Smith, D.J. & J. Campbell, 1988. Distribution of glutamine synthetase and carbamoyl-phosphate synthetase I in vertebrate liver. Proc. Natl. Acad. Sci. USA 85: 160–164.

    PubMed  Google Scholar 

  • Smith, D.J., N.M. Ritter & J.W. Campbell, 1987. Glutamine synthetase isozymes in elasmobranch brain and liver tissues. J. Biol. Chem. 262: 198–202.

    PubMed  Google Scholar 

  • Strand, D.J. & J.F. McDonald, 1989. Insertion of a copia element 5′ to theDrosophila melanoguster alcohol dehydrogenase gene (adh) is associated with altered developmental and tissue-specific patterns of expression. Genetics 121: 787–794.

    PubMed  Google Scholar 

  • Tapia, R., 1980. Glutamine metabolism in brain, pp. 285–297 in Glutamine: Metabolism, Enzymology, and Regulation, edited by J. Mora and R. Palacios. Academic Press, New York/London.

    Google Scholar 

  • Tingey, S., F. Tsai, J. Edwards, E. Walker & G. Coruzzi, 1988. Chloroplast and cytosolic glutamine synthetase are encoded by homologous nuclear genes which are differently expressed in vivo. J. Biol. Chem. 263: 9651–9657.

    PubMed  Google Scholar 

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Caggese, C., Barsanti, P., Viggiano, L. et al. Genetic, molecular and developmental analysis of the glutamine synthetase isozymes ofDrosophila melanogaster . Genetica 94, 275–281 (1994). https://doi.org/10.1007/BF01443441

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