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Protein Expression in Down Syndrome Brain pp 347–359Cite as

Reduction of nucleoside diphosphate kinase B, Rab GDP- dissociation inhibitor beta and histidine triad nucleotide-binding protein in fetal Down Syndrome brain

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Summary

Information on the various factors leading to impairments in the developing brain of fetal Down Syndrome patients is limited to few histological reports. We therefore attempted to describe expression levels of proteins in brain using the proteomic technique of two-dimensional electrophoresis with subsequent mass spectroscopical identification of protein spots and quantification with specific software. Cortical tissue was obtained from autopsy of human fetal abortus. Protein levels of GTP-binding nuclear protein ran, guanine nucleotide-binding protein g(o), alpha subunit 2, guanine nucleotide-binding protein g(i)/g(s)/g(t) beta subunit 1, -beta subunit 2, guanine nucleotide-binding protein beta subunit 5, nucleoside diphosphate kinase A, nucleoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta, Rho GDP-dissociation inhibitor 1, biphosphate 3′-nucleotidase, small glutamine-rich tetra-tricopeptide repeat-containing protein and histidine triad nucleotide-binding protein were studied.

Quantification revealed statistically significant reduced levels of nucleoside diphosphate kinase B, Rab GDP-dissociation inhibitor beta and histidine triad nucleotide-binding protein in fetal DS brain as compared to controls.

We conclude that in early prenatal life proteins involved in neural differentiation, migration and synaptic transmission are impaired in DS cortex. These results may help to understand the abundant mechanisms leading to abnormalities in the wiring, structure and function of DS brain.

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References

  • Agou F, Raveh S, Mesnildrey S, Veron S (1999) Single strand DNA specificity analysis of human nucleoside diphosphate kinase B. J Biol Chem 274: 19630–19636

    Article  PubMed  CAS  Google Scholar 

  • Backer J, Mendola C, Kovesdi I, Fairhurst J, O’Hara B, Eddy RL, Shows T, Mathew S, Murty V, Chaganti R (1993) Chromosomal localisation and nucleoside diphosphate kinase activity of human metastasis-suppressor genes NM23-1 and NM23-2. Oncogene 8: 497–502

    PubMed  CAS  Google Scholar 

  • Berndt P, Hobolm U, Langen H (1999) Reliable automatic protein identification from matrix-assisted laser desorption/ionisation mass spectrometric peptide fingerprints.Electrophoresis 20: 3521–3526

    Article  PubMed  CAS  Google Scholar 

  • Bradford M (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  • Brzoska P, Chen H, Levin N, Kuo WL, Collins C, Fu KK, Gray J, Christman M (1996) Cloning, mapping and in vivo localisation of a human member of the PKCI-1 protein family (PKCNH1). Genomics 36: 151–156

    Article  PubMed  CAS  Google Scholar 

  • D’Adamo P, Menegon A, Lo Nigro C, Grasso M, Tamanini F, Bienvenu T, Gedeon A,Oostra B, Wu SK, Tandon A, Valtorta F, Balch W, Chelly J, Toniolo D (1998) Mutations in GDI1 are responsible for X-linked non-specific mental retardation.Nature Genet 19: 134–139

    Article  PubMed  Google Scholar 

  • De la Monte S (1999) Molecular abnormalities of the brain in Down syndrome:relevance to Alzheimer’s neurodegeneration. J Neural Transm [Suppl] 57: 1–20

    Google Scholar 

  • Dierssen M, Vallina I, Baamonde C, Garcia-Calatayud S, Lumbreras M, Florez J (1997) Alterations of central noradrenergic transmission in Ts65Dn mouse, a model for Down syndrome. Brain Res 749: 238–244

    Article  PubMed  CAS  Google Scholar 

  • Epstein C (1995) The metabolic and molecular bases of inherited disease In: Scriver SR,Beaudet AL, Sly WS, Valle D (eds) Down Syndrome (Trisomy 21). McGraw Hill,New York, pp 749–794

    Google Scholar 

  • Fleig U, Salus S, Karig I, Sazer S (2000) The fission yeast ran GTPase is required for microtubule integrity. J Cell Biol 151: 1101–1112

    Article  PubMed  CAS  Google Scholar 

  • Fountoulakis M, Langen H (1997) Identification of proteins by matrix-assisted laser desorption ionisation-mass spectrometry following in-gel digestion in low-salt, non- volatile buffer and simplified peptide recovery. Anal Biochem 250: 153–156

    Article  PubMed  CAS  Google Scholar 

  • Fountoulakis M, Cairns N, Lubec G (1999) Increased levels of 14-3-3 gamma and epsilon proteins in brain of patients with Alzheimer’s disease and Down Syndrome. J Neural Transm [Suppl] 57: 323–335

    CAS  Google Scholar 

  • Fuentes J, Genesca L, Kingsbury T, Cunningham K, Perez-Riba M, Estivill X, de la Luna S (2000) DSCR1, over expressed in Down Syndrome, is an inhibitor of calcineurin-mediated signalling pathways. Hum Mol Genet 9: 1681–1690

    Article  PubMed  CAS  Google Scholar 

  • Gilman A (1987) G proteins: transducers of receptor-generated signals. Annu Rev Biochem 56: 615–649

    Article  PubMed  CAS  Google Scholar 

  • Glynn P (2000) Neural development and neurodegeneration: two faces of neuropathy target esterase. Prog Neurobiol 61: 61–74

    Article  PubMed  CAS  Google Scholar 

  • Joosten M, Vankan-Berkhoudt Y, Van den Broek M, Beijen A, Lowenberg B, von Lindern M, Deiwel R (2000) The gene NM23-M2 is frequently mutated in Leukemia.Exp Hematol 28: 1491

    Article  Google Scholar 

  • Kaziro Y (1978) The role of guanosine 5’-triphosphate in polypeptide chain elongation.Biochim Biophys Acta 505: 95–127

    Article  PubMed  CAS  Google Scholar 

  • Keim D, Hailat N, Melhem R, Zhu XX, Lascu I, Veron M, Strahler J, Hanasch S (1992) Proliferation-related expression of pl9/nm23 nucleoside diphosphate kinase. J Clin Invest 89: 919–924

    Article  PubMed  CAS  Google Scholar 

  • Korsisaari N, Mäkelä T (2000) Interaction of Cdk7 and Kin28 with Hint/PKCI-1 and Hntl Histidine triad proteins. J Biol Chem 275: 34837–34840

    Article  PubMed  CAS  Google Scholar 

  • Kraeft S, Traincart F, Bourdais J, Mesnildrey S, Veron M, Chen LB (1996) Nuclear localisation of nucleoside diphosphate kinase type B (nm23-H2) in cultured cells. Exp Cell Res 246: 355–367

    Google Scholar 

  • Langen H, Roder D, Juranville J, Fountoulakis M (1997) Effect of protein application mode and acrylamide concentration on the resolution of protein spots separated by two-dimensional gel electrophoresis. Electrophoresis 18: 2085–2090

    Article  PubMed  CAS  Google Scholar 

  • Lima C, Klein M, Hendrickson W (1997) Structure-based analysis of catalysis and substrate definition in the HIT protein family. Science 278: 286–290

    Article  PubMed  CAS  Google Scholar 

  • Nuoffer C, Davidson HW, Matteson J, Meinkoth J, Balch W (1994) A GDP-bound of rabl inhibits protein export from the endoplasmic reticulum and transport between Golgi compartments. J Cell Biol 125: 225–237

    Article  PubMed  CAS  Google Scholar 

  • Ohneda K, Fukuda M, Shimada N, Ishikawa N, Ichou T, Kaji K, Toyota T, Kimura N (1994) Increased expression of nucleoside diphosphate kinases/nm23 in human diploid fibroblasts transformed by SV40 large T antigen or 60Co irradiation. FEBS Lett 348: 273–277

    Article  PubMed  CAS  Google Scholar 

  • Okabe-Kado J, Kasukabe T, Hozumi M, Honma Y, Kimura N, Baba H, Urano T, Shiku H (1995) A new function of Nm23/NDP kinase as a differentiation inhibitory factor, which does not require its kinase activity. FEBS Lett 363: 311–315

    Article  PubMed  CAS  Google Scholar 

  • Postel E (1999) Cleavage of DNA by human NM23-H2/Nucleoside diphosphate kinase involves formation of a covalent protein-DNA complex. J Biol Chem 274: 22821–22829

    Article  PubMed  CAS  Google Scholar 

  • Postel E, Berberich S, Flint S, Ferrone C (1993) Human c-myc transcription factor PuF identified as nm23-H2 nucleoside diphosphate kinase, a candidate suppressor of tumor metastasis. Science 261: 478–480

    Article  PubMed  CAS  Google Scholar 

  • Postel E, Weiss V, Beneken J, Kirtane A (1996) Mutational analysis of NM23-H2/NDP kinase identifies the structural domains critical to recognition of a c-myc regulatory element. Proc Natl Acad Sci USA 93: 6892–6897

    Article  PubMed  CAS  Google Scholar 

  • Postel E, Abramczyk B, Levit M, Kyin S (2000) Catalysis of DNA cleavage and nucleoside triphosphate synthesis by NM″§-H2/NDP kinase share an active site that implies a DNA repair function. Proc Natl Acad Sci USA 97: 14194–14199

    Article  PubMed  CAS  Google Scholar 

  • Raveh S, Vinh J, Rossier J, Agou F, Veron M (2001) Peptidic determinants and structural model of human NDP kinase B (Nm23-H2) bound to single-stranded DNA. Biochem 40: 5882–5893

    Article  CAS  Google Scholar 

  • Razin E, Zhang ZC, Nechushtan H, Frenkel S, Lee YN, Arudchandran R, Rivera J (1999) Suppression of Microphthalmia transcriptional activity by its association with Protein kinase C-interacting Protein 1 in mastcells. J Biol Chem 274: 34272–34276

    Article  PubMed  CAS  Google Scholar 

  • Reed W, Ozand P (1985) Adrenergic sensitivity of cultured murine trisomy 16 cells. Dev Pharmacol Ther 8: 200–208

    PubMed  CAS  Google Scholar 

  • Roymans D, Willems R, Vissenberg K, De Jonghe C, Grobben B, Claes P, Lascu I, Van Bockstaele D, Verbelen J, Van Broeckhoven C, Siegers H (2000) Nucleoside diphosphate kinase beta (Nm23-Rl/NDPKbeta) is associated with intermediate filaments and becomes upregulated upon cAMP-induced differentiation of rat C6 glioma. Exp Cell Res 261: 127–138

    Article  PubMed  CAS  Google Scholar 

  • Sanes JR, Jessell TM (2000) The guidance of axons to their targets. In: Kandel ER, Schwartz JH, Jessell TM (eds) Principles of neural science. McGraw Hill, New York, pp 1063–1086

    Google Scholar 

  • Schimmoller F, Simon I, Pfeffer S (1998) Rab GTPases, Directors of vesicle docking. J Biol Chem 273: 22161–22164

    Article  PubMed  CAS  Google Scholar 

  • Schubert P, Morino T, Miyazaki H, Ogata T, Nakamura Y, Marchini C, Ferroni S (2000) Cascading glia reactions: a common pathomechanism and its differentiated control by cyclic nucleotide signalling. Ann NY Acad Sci 903: 24–33

    Article  PubMed  CAS  Google Scholar 

  • Siprashvili Z, Sozzi G, Barnes L, Mc Cue P, Robinson A, Eryomin V, Sard L, Tagliabue E, Greco A, Fusetti L, Schwartz G, Pierotti M, Croce C, Huebner K (1997) Replacement of FHIT in cancer cells suppresses tumorigenicity. Proc Natl Acad Sci USA 94: 13771–13776

    Article  PubMed  CAS  Google Scholar 

  • Shisheva A, Chinni S, DeMarco C (1999) general role of GDP Dissociation Inhibitor 2 in membrane release of Rab proteins: modulation of its functional interactions by in vitro and in vivo structural modifications. Biochem 38: 11711–11721

    Article  CAS  Google Scholar 

  • Spiegelberg B, Xiong JP, Smith JJ, Gu R, York J (1999) Cloning and characterization of a mammalian lithium-sensitive bisphosphate 3’-nucleotidase inhibited by inositol 1,4-bisphosphate. J Biol Chem 274: 13619–13628

    Article  PubMed  CAS  Google Scholar 

  • Stahl J, Leone A, Rosengard A, Porter L, King C, Steeg P (1991) Identification of a second human nm23 gene, nm23-H2. Cancer Res 51: 445–449

    PubMed  CAS  Google Scholar 

  • Takai Y, Sasaki T, Matozaki T (2001) Small GTP-binding proteins. Physiol Rev 81: 153–208

    PubMed  CAS  Google Scholar 

  • Venturelli D, Martinez R, Melotti P, Casella I, Peschle C, Cucco C, Spampinato G, Darzynkiewicz Z, Calabretta B (1995) Overexpression of DR-nm23, a protein encoded by a member of the nm23 gene family, inhibits granulocyte differentiation and induces apoptosis in 32Dcl3 myeloid cells. Proc Natl Acad Sci USA 92: 7435–7439

    Article  PubMed  CAS  Google Scholar 

  • Wisniewski K, Kida E (1994) Abnormal neurogenesis and synaptogenesis in Down Syndrome brain. Dev Brain Dysfunct 7: 289–301

    Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, University of Vienna, Vienna, Austria

    R. Weitzdoerfer, D. Stolzlechner & G. Lubec

  2. Medical and Molecular Genetics Center-IRO, Hospital Duran i Reynals, Barcelona, Spain

    M. Dierssen & J. Ferreres

  3. Gene Technologies, F. Hoffmann-La Roche, Basel, Switzerland

    M. Fountoulakis

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  1. R. Weitzdoerfer
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  2. D. Stolzlechner
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  3. M. Dierssen
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  4. J. Ferreres
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  5. M. Fountoulakis
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  6. G. Lubec
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Editors and Affiliations

  1. Universität-Kinderklinik, Währinger Gürtel 18-20, A-1090, Wien, Austria

    Gert Lubec

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© 2001 Springer-Verlag/Wien

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Weitzdoerfer, R., Stolzlechner, D., Dierssen, M., Ferreres, J., Fountoulakis, M., Lubec, G. (2001). Reduction of nucleoside diphosphate kinase B, Rab GDP- dissociation inhibitor beta and histidine triad nucleotide-binding protein in fetal Down Syndrome brain. In: Lubec, G. (eds) Protein Expression in Down Syndrome Brain. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6262-0_29

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  • DOI: https://doi.org/10.1007/978-3-7091-6262-0_29

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83704-7

  • Online ISBN: 978-3-7091-6262-0

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