Abstract
Early maternal infections with Neisseria gonorrhoeae (NG) correlate to an increased lifetime schizophrenia risk for the offspring, which might be due to an immune-mediated mechanism. Here, we investigated the interactions of polyclonal antisera to NG (α-NG) with a first trimester prenatal brain multiprotein array, revealing among others the SNARE-complex protein Snap23 as a target antigen for α-NG. This interaction was confirmed by Western blot analysis with a recombinant Snap23 protein, whereas the closely related Snap25 failed to interact with α-NG. Furthermore, a polyclonal antiserum to the closely related bacterium Neisseria meningitidis (α-NM) failed to interact with both proteins. Functionally, in SH-SY5Y cells, α-NG pretreatment interfered with both insulin-induced vesicle recycling, as revealed by uptake of the fluorescent endocytosis marker FM1-43, and insulin-dependent membrane translocation of the glucose transporter GluT4. Similar effects could be observed for an antiserum raised directly to Snap23, whereas a serum to Snap25 failed to do so. In conclusion, Snap23 seems to be a possible immune target for anti-gonococcal antibodies, the interactions of which seem at least in vitro to interfere with vesicle-associated exocytosis. Whether these changes contribute to the correlation between maternal gonococcal infections and psychosis in vivo remains still to be clarified.
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Babulas V, Factor-Litvak P, Goetz R, Schaefer CA, Brown AS (2006) Prenatal exposure to maternal genital and reproductive infections and adult schizophrenia. Am J Psychiatry 163:927–929
Bassani S, Cingolani LA, Valnegri P, Folci A, Zapata J, Gianfelice A, Sala C, Goda Y, Passafaro M (2012) The X-linked intellectual disability protein TSPAN7 regulates excitatory synapse development and AMPAR trafficking. Neuron 73:1143–1158
Ben-Hur H, Gurevich P, Elhayany A, Avinoach I, Schneider DF, Zusman I (2005) Transport of maternal immunoglobulins through the human placental barrier in normal pregnancy and during inflammation. Int J Mol Med 16:401–407
Ben Jilani KE, Panee J, He Q, Berry MJ, Li PA (2007) Overexpression of selenoprotein H reduces Ht22 neuronal cell death after UVB irradiation by preventing superoxide formation. Int J Biol Sci 3:198–204
Benomar Y, Naour N, Aubourg A, Bailleux V, Gertler A, Djiane J, Guerre-Millo M, Taouis M (2006) Insulin and leptin induce Glut4 plasma membrane translocation and glucose uptake in a human neuronal cell line by a phosphatidylinositol 3-kinase-dependent mechanism. Endocrinology 147:2550–2556
Bogan JS (2012) Regulation of glucose transporter translocation in health and diabetes. Annu Rev Biochem 81:507–532
Boyd KN, Mailman RB (2015) Dopamine receptor signaling and current and future antipsychotic drugs. Handb Exp Pharmacol 212:53–86
Burk RF, Hill KE (2005) Selenoprotein P: an extracellular protein with unique physical characteristics and a role in selenium homeostasis. Annu Rev Nutr 25:215–235
Büssow K, Cahill D, Nietfeld W, Bancroft D, Scherzinger E, Lehrach H, Walter G (1998) A method for global protein expression and antibody screening on high-density filters of an arrayed cDNA library. Nucleic Acids Res 26:5007–5008
Büssow K, Nordhoff E, Lübbert C, Lehrach H, Walter G (2000) A human cDNA library for high-throughput protein expression screening. Genomics 65:1–8
Cannon M, Jones P (1996) Schizophrenia. J Neurol Neurosurg Psychiatry 60:604–613
Cepok S, Zhou D, Srivastava R, Nessler S, Stei S, Büssow K, Sommer N, Hemmer B (2005) Identification of Epstein-Barr virus proteins as putative targets of the immune response in multiple sclerosis. J Clin Invest 115:1352–1360
Chowdhury HH, Jevsek M, Kreft M, Mars T, Zorec R, Grubic Z (2005) Insulin-induced exocytosis in single, in vitro innervated human muscle fibres: a new approach. Pflugers Arch 450:131–135
Collins J (1957) Insulin resistance in schizophrenia. Med J Aust 44:467–470
Dahm L, Klugmann F, Gonzalez-Algaba A, Reuss B (2010) Tamoxifen and raloxifene modulate gap junction coupling during early phases of retinoic acid-dependent neuronal differentiation of NTera2/D1 cells. Cell Biol Toxicol 26:579–591
Edwards JL, Butler EK (2011) The pathobiology of Neisseria gonorrhoeae lower female genital tract infection. Front Microbiol 2:102
El Messari S, Leloup C, Quignon M, Brisorgueil MJ, Penicaud L, Arluison M (1998) Immunocytochemical localization of the insulin-responsive glucose transporter 4 (GluT4) in the rat central nervous system. J Comp Neurol 399:492–512
Foster LJ, Yaworsky K, Trimble WS, Klip A (1999) SNAP23 promotes insulin-dependent glucose uptake in 3T3-L1 adipocytes: possible interaction with cytoskeleton. Am J Phys 276:C1108–C1114
Gaffield MA, Betz WJ (2006) Imaging synaptic vesicle exocytosis and endocytosis with FM dyes. Nat Protocols 1:2916–2921
Gannon NP, Conn CA, Vaughan RA (2015) Dietary stimulators of GLUT4 expression and translocation in skeletal muscle: a mini-review. Mol Nutr Food Res 59:48–64
Giusti-Rodríguez P, Sullivan PF (2013) The genomics of schizophrenia: update and implications. J Clin Invest 123:4557–4563
Grassi D, Plonka FB, Oksdath M, Guil AN, Sosa LJ, Quiroga S (2015) Selected SNARE proteins are essential for the polarized membrane insertion of igf-1 receptor and the regulation of initial axonal outgrowth in neurons. Cell Discov 1:15023
Grusovin J, Macaulay SL (2003) Snares for GLUT4—mechanisms directing vesicular trafficking of GLUT4. Front Biosci 8:d620–d641
Guyon T, Wakkach A, Poea S, Mouly V, Klingel-Schmitt I, Levasseur P, Beeson D, Asher O, Tzartos S, Berrih-Aknin S (1998) Regulation of acetylcholine receptor gene expression in human myasthenia gravis muscles. Evidences for a compensatory mechanism triggered by receptor loss. J Clin Invest 102:249–263
Harland R, Antonova E, Owen GS, Broome M, Landau S, Deeley Q, Murray R (2009) A study of psychiatrists’ concepts of mental illness. Psychol Med 39:967–976
Harrison PJ (1999) The neuropathology of schizophrenia. A critical review of the data and their interpretation. Brain 122:593–624
Hemby SE, Ginsberg SD, Brunk B, Arnold SE, Trojanowski JQ, Eberwine JH (2002) Gene expression profile for schizophrenia: discrete neuron transcription patterns in the entorhinal cortex. Arch Gen Psychiatry 59:631–640
Hemler ME (2005) Tetraspanin functions and associated microdomains. Nat Rev Mol Cell Biol 6:801–811
Henkel AW, Bieger SC (1994) Quantification of proteins dissolved in an electrophoresis sample buffer. Anal Biochem 223:329–331
Hepp R, Perraut M, Chasserot-Golaz S, Galli T, Aunis D, Langley K, Grant NJ (1999) Cultured glial cells express the SNAP-25 analogue SNAP-23. Glia 27:181–187
Hoffman TA, Damus AJ, Sands L (1979) Evaluation of a gonococcal serologic test. Am J Clin Pathol 71:184–189
Holt LJ, Büssow K, Walter G, Tomlinson IM (2000) By-passing selection: direct screening for antibody-antigen interactions using protein arrays. Nucleic Acids Res 28:E72
Hope S, Melle I, Aukrust P, Steen NE, Birkenaes AB, Lorentzen S, Agartz I, Ueland T, Andreassen OA (2009) Similar immune profile in bipolar disorder and schizophrenia: selective increase in soluble tumor necrosis factor receptor I and von Willebrand factor. Bipolar Disord 11:726–734
Horn S, Lueking A, Murphy D, Staudt A, Gutjahr C, Schulte K, König A, Landsberger M, Lehrach H, Felix SB, Cahill DJ (2006) Profiling humoral autoimmune repertoire of dilated cardiomyopathy (DCM) patients and development of a disease-associated protein chip. Proteomics 6:605–613
Hosák L, Silhan P, Hosáková J (2012) Genome-wide association studies in schizophrenia, and potential etiological and functional implications of their results. Acta Med (Hradec Kralove) 55:3–11
Iorio R, Lennon VA (2012) Neural antigen-specific autoimmune disorders. Immunol Rev 248:104–121
Kahl KG, Georgi K, Bleich S, Muschler M, Hillemacher T, Hilfiker-Kleinert D, Schweiger U, Ding X, Kotsiari A, Frieling H (2016) Altered DNA methylation of glucose transporter 1 and glucose transporter 4 in patients with major depressive disorder. J Psychiatr Res 76:66–73
Kahn RS, Sommer IE (2015) The neurobiology and treatment of first-episode schizophrenia. Mol Psychiatry 20:84–97
Kawaguchi T, Tamori Y, Kanda H, Yoshikawa M, Tateya S, Nishino N, Kasuga M (2010) The t-SNAREs syntaxin4 and SNAP23 but not v-SNARE VAMP2 are indispensable to tether GLUT4 vesicles at the plasma membrane in adipocyte. Biochem Biophys Res Commun 391:1336–1341
Kawanishi M, Tamori Y, Okazawa H, Araki S, Shinoda H, Kasuga M (2000) Role of SNAP23 in insulin-induced translocation of GLUT4 in 3T3-L1 adipocytes. Mediation of complex formation between syntaxin4 and VAMP2. J Biol Chem 275:8240–8247
Khandaker GM, Zimbron J, Lewis G, Jones PB (2013) Prenatal maternal infection, neurodevelopment and adult schizophrenia: a systematic review of population-based studies. Psychol Med 43:239–257
Kijanka G, Murphy D (2009) Protein arrays as tools for serum autoantibody marker discovery in cancer. J Proteome 72:936–944
Kobayashi M, Nikami H, Morimatsu M, Saito M (1996) Expression and localization of insulin-regulatable glucose transporter (GLUT4) in rat brain. Neurosci Lett 213:103–106
Kohrle J (2005) Selenium and the control of thyroid hormone metabolism. Thyroid 15:841–853
Kryukov GV, Castellano S, Novoselov SV, Lebanov AV, Zehtab O, Guigo R, Gladyshev VN (2003) Characterization of mammalian selenoproteomes. Science 300:1439–1443
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685
Lang T, Jahn R (2008) Core proteins of the secretory machinery. Handb Exp Pharmacol 184:107–127
Lindenmayer JP, Nathan AM, Smith RC (2001) Hyperglycemia associated with the use of atypical antipsychotics. J Clin Psychiatry 62(Suppl 23):30–38
Masopust J, Malý R, Andrýs C, Vališ M, Bažant J, Hosák L (2011) Markers of thrombogenesis are activated in unmedicated patients with acute psychosis: a matched case control study. BMC Psychiatry 11:2/1–2/5
Melkersson KI, Hulting AL, Brismar KE (1999) Different influences of classical antipsychotics and clozapine on glucose-insulin homeostasis in patients with schizophrenia or related psychoses. J Clin Psychiatry 60:783–791
Meltzer HY, Stahl SM (1976) The dopamine hypothesis of schizophrenia: a review. Schizophr Bull 2:19–76
Murray RM, O'Callaghan E, Castle DJ, Lewis SW (1992) A neurodevelopmental approach to the classification of schizophrenia. Schizophr Bull 18:319–332
Noll R (2004) Historical review: autointoxication and focal infection theories of dementia praecox. World J Biol Psychiatry 5:66–72
Noll R (2007) Kraepelin’s ‘lost biological psychiatry’? Autointoxication, organotherapy and surgery for dementia praecox. Hist Psychiatry 18:301–320
Novoselov SV, Kryukov GV, Xu XM, Carlson BA, Hatfield DL, Gladyshev VN (2007) Selenoprotein H is a nucleolar thioredoxin-like protein with a unique expression pattern. J Biol Chem 282:11960–11968
Piton A, Gauthier J, Hamdan FF, Lafreniere RG, Yang Y, Henrion E, Laurent S, Noreau A, Thibodeau P, Karemera L, Spiegelman D, Kuku F, Duguay J, Destroismaisons L, Jolivet P, Cote M, Lachapelle K, Diallo O, Raymond A, Marineau C, Champagne N, Xiong L, Gaspar C, Riviere JB, Tarabeux J, Cossette P, Krebs MO, Rapoport JL, Addington A, DeLisi LE, Mottron L, Joober R, Fombonne E, Drapeau P, Rouleau GA (2011) Systematic resequencing of X-chromosome synaptic genes in autism spectrum disorder and schizophrenia. Mol Psychiatry 16:867–880
Ramsby ML, Makowski GS, Khairallah EA (1994) Differential detergent fractionation of isolated hepatocytes: biochemical, immunochemical and two-dimensional gel electrophoresis characterization of cytoskeletal and noncytoskeletal compartments. Electrophoresis 15:265–277
Rayman MP (2000) The importance of selenium to human health. Lancet 356:233–241
Reuss B (2014) Antibodies directed to Neisseria gonorrhoeae impair nerve growth factor-dependent neurite outgrowth in rat PC12 cells. J Mol Neurosci 52:353–365
Reuss B, Asif AR (2014) Antibodies directed to the gram-negative bacterium Neisseria gonorrhoeae cross-react with the 60 kDa heat shock protein and lead to impaired neurite outgrowth in NTera2/D1 cells. J Mol Neurosci 54:125–136
Reuss B, Schroten H, Ishikawa H, Asif AR (2015) Cross-reactivity of antibodies directed to the gram-negative bacterium Neisseria gonorrhoeae with heat shock protein 60 and ATP-binding protein correlates to reduced mitochondrial activity in HIBCPP choroid plexus papilloma cells. J Mol Neurosci 57:123–138
Ripke S et al., (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511:421–427
Saito Y, Takahashi K (2002) Characterization of selenoprotein P as a selenium supply protein. Eur J Biochem 269:5746–5751
Schimmelbusch WH, Mueller PS, Sheps J (1971) The positive correlation between insulin resistance and duration of hospitalization in untreated schizophrenia. Br J Psychiatry 118:429–436
Sørensen HJ, Mortensen EL, Reinisch JM, Mednick SA (2009) Association between prenatal exposure to bacterial infection and risk of schizophrenia. Schizophrenia Bull 35:631–637
Strauss JA, Shaw CS, Bradley H, Wilson OJ, Dorval T, Pilling J, Wagenmakers AJ (2016) Immunofluorescence microscopy of SNAP23 in human skeletal muscle reveals colocalization with plasma membrane, lipid droplets, and mitochondria. Physiol Rep 4:e12662
Suh YH, Terashima A, Petralia RS, Wenthold RJ, Isaac JT, Roche KW, Roche PA (2010) A neuronal role for SNAP-23 in postsynaptic glutamate receptor trafficking. Nat Neurosci 13:338–343
Suh YH, Yoshimoto-Furusawa A, Weih KA, Tessarollo L, Roche KW, Mackem S, Roche PA (2011) Deletion of SNAP-23 results in pre-implantation embryonic lethality in mice. PLoS One 6:e18444
Tandon R, Nasrallah HA, Keshavan MS (2009) Schizophrenia, “just the facts” 4. Clinical features and conceptualization. Schizophr Res 110:1–23
Vannucci SJ, Koehler-Stec ME, Li K, Reynolds HR, Clark R, Simpson IA (1998) GluT4 glucose transporterexpression in rodent brain: effect of diabetes. Brain Res 797:1–11
Verma SK, Subramaniam M, Liew A, Poon LY (2009) Metabolic risk factors in drug-naive patients with first-episode psychosis. J Clin Psychiatry 70:997–1000
Wang Y, Tang BL (2006) SNAREs in neurons—beyond synaptic vesicle exocytosis. Mol Membr Biol 23:377–384
Washbourne P, Liu XB, Jones EG, McAllister AK (2004) Cycling of NMDA receptors during trafficking in neurons before synapse formation. J Neurosci 24:8253–8264
Winocur G, Greenwood CE, Piroli GG, Grillo CA, Reznikov LR, Reagan LP, McEwen BS (2005) Memory impairment in obese Zucker rats: an investigation of cognitive function in an animal model of insulin resistance and obesity. Behav Neurosci 119:1389–1395
Zabel C, Klose J (2009) Protein extraction for 2DE. Methods Mol Biol 519:171–196
Zhu QM, Yamakuchi M, Lowenstein CJ (2015) SNAP23 regulates endothelial exocytosis of von Willebrand factor. PLoS One 10:e0118737
Zylbersztejn K, Galli T (2011) Vesicular traffic in cell navigation. FEBS J 278:4497–4505
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We would like to thank the University Medicine Göttingen (UMG) for persistent and reliable support of our work.
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Almamy, A., Schwerk, C., Schroten, H. et al. Crossreactivity of an Antiserum Directed to the Gram-Negative Bacterium Neisseria gonorrhoeae with the SNARE-Complex Protein Snap23 Correlates to Impaired Exocytosis in SH-SY5Y Cells. J Mol Neurosci 62, 163–180 (2017). https://doi.org/10.1007/s12031-017-0920-2
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DOI: https://doi.org/10.1007/s12031-017-0920-2