Skip to main content

Advertisement

SpringerLink
Log in

Analysis of amyloid precursor protein function in Drosophila melanogaster

  • Review
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

Amyloid precursor proteins (APPs) are evolutionary conserved from nematodes to man (Jacobsen and Iverfeldt in Cell Mol Life Sci 66:2299–2318, 2009) suggesting an important physiological function of these proteins. Human APP is a key factor in the pathogenesis of Alzheimer’s Disease because its proteolytic processing results in the production of the neurotoxic Aβ-peptide, which accumulates in the amyloid plaques characteristic for this disease (Selkoe in Physiol Rev 81(2):741–766, 2001). However, the processing also leads to the production of several other fragments and the role of these products, as well as the function of the full-length protein is so far not well understood. The functional analysis of APP in vertebrates has been hampered by the fact that two close relatives, APLP1 and APLP2, exist and that knock-out mice for APP only show subtle defects. In contrast, invertebrates like Caenorhabditis elegans and Drosophila express only one APP-like protein but whereas a null mutation in the C. elegans APL-1 protein is lethal, flies lacking APPL (Amyloid Precursor Protein-like) are viable but show synaptic defects and behavioral abnormalities. Together with the analyses of flies that express APP proteins ectoptically or xenotopically, these studies show that APP proteins are involved in neuronal differentiation, neuritic outgrowth, and synapse formation. In addition, they play a role in long-term memory formation and maintaining brain integrity in adult flies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Araki W, Kitaguchi N, Tokushima Y, Ishii K, Aratake H, Shimohama S, Nakamura S, Kimura J (1991) Trophic effect of beta-amyloid precursor protein on cerebral cortical neurons in culture. Biochem Biophys Res Commun 181(1):265–271

    Article  PubMed  CAS  Google Scholar 

  • Ashley J, Packard M, Ataman B, Budnik V (2005) Fasciclin II signals new synapse formation through amyloid precursor protein and the scaffolding protein dX11/Mint. J Neurosci 25(25):5943–5955

    Article  PubMed  CAS  Google Scholar 

  • Aso Y, Grübel K, Busch S, Friedrich AB, Siwanowicz I, Tanimoto H (2009) The mushroom body of adult Drosophila characterized by GAL4 drivers. J Neurogenet 23(1–2):156–172

    Article  PubMed  CAS  Google Scholar 

  • Benzer S (1967) Behavioral mutants of Drosophila isolated by countercurrent distribution. Proc Natl Acad Sci USA 58(3):1112–1119

    Article  PubMed  CAS  Google Scholar 

  • Bilen J, Bonini NM (2005) Drosophila as a model for human neurodegenerative disease. Annu Rev Genet 39:153–171

    Article  PubMed  CAS  Google Scholar 

  • Boulianne GL, Livne-Bar I, Humphreys JM, Liang Y, Lin C, Rogaev E, St. George-Hyslop P (1997) Cloning and characterization of the Drosophila presenilin homologue. Neuroreport 8(4):1025–1029

    Article  PubMed  CAS  Google Scholar 

  • Brou C, Logeat F, Gupta N, Bessia C, LeBail O, Doedens JR, Cumano A, Roux P, Black RA, Israël A (2000) A novel proteolytic cleavage involved in Notch signaling: the role of the disintegrin-metalloprotease TACE. Mol Cell 5:207–216

    Article  PubMed  CAS  Google Scholar 

  • Cao X, Südhof TC (2001) A transcriptionally active complex of APP with Fe65 and histone acetyltransferase Tip60. Science 293(5527):115–120

    Article  PubMed  CAS  Google Scholar 

  • Carmine-Simmen K, Proctor T, Tschäpe J, Poeck B, Triphan T, Strauss R, Kretzschmar D (2009) Neurotoxic effects induced by the Drosophila amyloid-beta peptide suggest a conserved toxic function. Neurobiol Dis 33(2):274–281

    Article  PubMed  CAS  Google Scholar 

  • Clark RF, Hutton M, Fuldner M, Froelich S, Karran E, Alzheimer’s disease collaborative group et al (1995) The structure of the presenilin 1 (S182) gene and identification of six novel mutations in early onset AD families. Nat Genet 11(2):219–222

    Article  CAS  Google Scholar 

  • Coulson EJ, Paliga K, Beyreuther K, Masters CL (2000) What the evolution of the amyloid protein precursor supergene family tells us about its function. Neurochem Int 36(3):175–184

    Article  PubMed  CAS  Google Scholar 

  • Daigle I, Li C (1993) apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor. Proc Natl Acad Sci USA 90(24):12045–12049

    Article  PubMed  CAS  Google Scholar 

  • De Strooper B, Annaert W (2010) Novel research horizons for presenilins and γ-secretases in cell biology and disease. Annu Rev Cell Dev Biol 26:235–260

    Article  PubMed  CAS  Google Scholar 

  • De Strooper B, Saftig P, Craessaerts K, Vanderstichele H, Guhde G, Annaert W, Von Figura K, Van Leuven F (1989) Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391(6665):387–390

    Article  CAS  Google Scholar 

  • Fossgreen A, Brückner B, Czech C, Masters CL, Beyreuther K, Paro R (1998) Transgenic Drosophila expressing human amyloid precursor protein show gamma-secretase activity and a blistered-wing phenotype. Proc Natl Acad Sci USA 95(23):13703–13708

    Article  PubMed  CAS  Google Scholar 

  • Francis R, McGrath G, Zhang J, Ruddy DA, Sym M, Apfeld J, Nicoll M, Maxwell M, Hai B, Ellis MC, Parks AL, Xu W, Li J, Gurney M, Myers RL, Himes CS, Hiebsch R, Ruble C, Nye JS, Curtis D (2002) aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase cleavage of betaAPP, and presenilin protein accumulation. Dev Cell 3(1):85–97

    Article  PubMed  CAS  Google Scholar 

  • Furukawa K, Barger SW, Blalock EM, Mattson MP (1996) Activation of K+ channels and suppression of neuronal activity by secreted beta-amyloid-precursor protein. Nature 379(6560):74–78

    Article  PubMed  CAS  Google Scholar 

  • Glenner GG, Wong CW (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120(3):885–890

    Article  PubMed  CAS  Google Scholar 

  • Goguel V, Belair AL, Ayaz D, Lampin-Saint-Amaux A, Scaplehorn N, Hassan BA, Preat T (2011) Drosophila amyloid precursor protein-like is required for long-term memory. J Neurosci 31(3):1032–1037

    Article  PubMed  CAS  Google Scholar 

  • Goldgaber D, Lerman MI, McBride OW, Saffiotti U, Gajdusek DC (1987) Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer’s disease. Science 235(4791):877–880

    Article  PubMed  CAS  Google Scholar 

  • Goodman Y, Mattson MP (1994) Secreted forms of beta-amyloid precursor protein protect hippocampal neurons against amyloid beta-peptide-induced oxidative injury. Exp Neurol 128(1):1–12

    Article  PubMed  CAS  Google Scholar 

  • Goutte C, Hepler W, Mickey KM, Priess JR (2000) aph-2 encodes a novel extracellular protein required for GLP-1-mediated signaling. Development 127(11):2481–2492

    PubMed  CAS  Google Scholar 

  • Gramates LS, Budnik V (1999) Assembly and maturation of the Drosophila larval neuromuscular junction. Int Rev Neurobiol 43:93–117

    Article  PubMed  CAS  Google Scholar 

  • Greeve I, Kretzschmar D, Tschäpe JA, Beyn A, Brellinger C, Schweizer M, Nitsch RM, Reifegerste R (2004) Age-dependent neurodegeneration and Alzheimer-amyloid plaque formation in transgenic Drosophila. J Neurosci 24(16):3899–3906

    Article  PubMed  CAS  Google Scholar 

  • Guo M, Hong EJ, Fernandes J, Zipursky SL, Hay BA (2003) A reporter for amyloid precursor protein gamma-secretase activity in Drosophila. Hum Mol Genet 12(20):2669–2678

    Article  PubMed  CAS  Google Scholar 

  • Hase M, Yagi Y, Taru H, Tomita S, Sumioka A, Hori K, Miyamoto K, Sasamura T, Nakamura M, Matsuno K, Suzuki T (2002) Expression and characterization of the Drosophila X11-like/mint protein during neural development. J Neurochem 81(6):1223–1232

    Article  PubMed  CAS  Google Scholar 

  • Heisenberg M (2003) Mushroom body memoir: from maps to models. Nat Rev Neurosci 4(4):266–275

    Article  PubMed  CAS  Google Scholar 

  • Hong CS, Koo EH (1997) Isolation and characterization of Drosophila presenilin homolog. Neuroreport 8(3):665–668

    Article  PubMed  CAS  Google Scholar 

  • Hornsten A, Lieberthal J, Fadia S, Malins R, Ha L, Xu X, Daigle I, Markowitz M, O’Connor G, Plasterk R, Li C (2007) APL-1, a Caenorhabditis elegans protein related to the human beta-amyloid precursor protein, is essential for viability. Proc Natl Acad Sci USA 104(6):1971–1976

    Article  PubMed  CAS  Google Scholar 

  • Hussain I, Powell D, Howlett DR, Tew DG, Meek TD, Chapman C, Gloger IS, Murphy KE, Southan CD, Ryan DM, Smith TS, Simmons DL, Walsh FS, Dingwall C, Christie G (1999) Identification of a novel aspartic protease (Asp 2) as beta-secretase. Mol Cell Neurosci 14:419–427

    Google Scholar 

  • Jacobsen KT, Iverfeldt K (2009) Amyloid precursor protein and its homologues: a family of proteolysis-dependent receptors. Cell Mol Life Sci 66:2299–2318

    Article  PubMed  CAS  Google Scholar 

  • Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, Multhaup G, Beyreuther K, Müller-Hill B (1987) The precursor of alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 325(6106):733–736

    Article  PubMed  CAS  Google Scholar 

  • Keene AC, Waddell S (2007) Drosophila olfactory memory: single genes to complex neural circuits. Nat Rev Neurosci 8(5):341–354

    Article  PubMed  CAS  Google Scholar 

  • Kemp BE, Mitchelhill KI, Stapleton D, Michell BJ, Chen ZP, Witters LA (1999) Dealing with energy demand: the AMP-activated protein kinase. Trends Biochem Sci 24(1):22–25

    Article  PubMed  CAS  Google Scholar 

  • Kim HJ, Kim SH, Shim SO, Park E, Kim C, Kim K, Tanouye MA, Yim J (2007) Drosophila homolog of APP-BP1 (dAPP-BP1) interacts antagonistically with APPL during Drosophila development. Cell Death Differ 14(1):103–115

    Article  PubMed  CAS  Google Scholar 

  • Kimberly WT, Zheng JB, Guénette SY, Selkoe DJ (2001) The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner. J Biol Chem 276(43):40288–40292

    PubMed  CAS  Google Scholar 

  • Kotani N, Kitazume S, Kamimura K, Takeo S, Aigaki T, Nakato H, Hashimoto Y (2005) Characterization of Drosophila aspartic proteases that induce the secretion of a Golgi-resident transferase, heparan sulfate 6-O-sulfotransferase. J Biochem 137(3):315–322

    Article  PubMed  CAS  Google Scholar 

  • Krashes MJ, Keene AC, Leung B, Armstrong JD, Waddell S (2007) Sequential use of mushroom body neuron subsets during Drosophila odor memory processing. Neuron 53(1):103–115

    Article  PubMed  CAS  Google Scholar 

  • Lai EC, Orgogozo V (2004) A hidden program in Drosophila peripheral neurogenesis revealed: fundamental principles underlying sensory organ diversity. Dev Biol 269(1):1–17

    Article  PubMed  CAS  Google Scholar 

  • Lammich S, Kojro E, Postina R, Gilbert S, Pfeiffer R, Jasionowski M, Haass C, Fahrenholz F (1999) Constitutive and regulated alpha-secretase cleavage of alzheimer’s amyloid precursor protein by a disintegrin metalloprotease. Proc Natl Acad Sci USA 96(7):3922–3927

    Article  PubMed  CAS  Google Scholar 

  • Leyssen M, Ayaz D, Hebert SS, Reeve S, De Strooper B, Hassan BA (2005) Amyloid precursor protein promotes post-developmental neurite arborization in the Drosophila brain. EMBO J 24(16):2944–2955

    Article  PubMed  CAS  Google Scholar 

  • Li Y, Liu T, Peng Y, Yuan C, Guo A (2004) Specific functions of Drosophila amyloid precursor-like protein in the development of nervous system and non-neural tissues. J Neurobiol 61(3):343–358

    Article  PubMed  CAS  Google Scholar 

  • Lichtenthaler SF (2011) Alpha-secretase in alzheimer’s disease: molecular identity, regulation and therapeutic potential. J Neurochem 116(1):10–21

    Article  PubMed  CAS  Google Scholar 

  • Link CD (2005) Invertebrate models of alzheimer’s disease. Genes Brain Behav 4(3):147–156

    Article  PubMed  CAS  Google Scholar 

  • Lorent K, Overbergh L, Moechars D, De Strooper B, Van Leuven F, Van den Berghe H (1995) Expression in mouse embryos and in adult mouse brain of three members of the amyloid precursor protein family, of the alpha-2-macroglobulin receptor/low density lipoprotein receptor-related protein and of its ligands apolipoprotein E, lipoprotein lipase, alpha-2-macroglobulin and the 40,000 molecular weight receptor-associated protein. Neuroscience 65(4):1009–1025

    Article  PubMed  CAS  Google Scholar 

  • Luo LQ, Martin-Morris L, White K (1990) Identification, secretion, and neural expression of APPL, a Drosophila protein similar to human amyloid protein precursor. J Neurosci 10(12):3849–3861

    Google Scholar 

  • Luo L, Tully T, White K (1992) Human amyloid precursor protein ameliorates behavioral deficit of flies deleted for Appl gene. Neuron 9:595–605

    Article  PubMed  CAS  Google Scholar 

  • Martin-Morris L, White K (1990) The Drosophila transcript encoded by the β-amyloid protein precursor-like gene is restricted to the nervous system. Development 110(1):185–195

    PubMed  CAS  Google Scholar 

  • Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in alzheimer disease and down syndrome. Proc Natl Acad Sci USA 82(12):4245–4249

    Article  PubMed  CAS  Google Scholar 

  • Mattson MP, Cheng B, Culwell AR, Esch FS, Lieberburg I, Rydel RE (1993) Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the beta-amyloid precursor protein. Neuron 10(2):243–254

    Article  PubMed  CAS  Google Scholar 

  • Merdes G, Soba P, Loewer A, Bilic MV, Beyreuther K, Paro R (2004) Interference of human and Drosophila APP and APP-like proteins with PNS development in Drosophila. EMBO J 23(20):4082–4095

    Article  PubMed  CAS  Google Scholar 

  • Müller U, Cristina N, Li ZW, Wolfer DP, Lipp HP, Rülicke T, Brandner S, Aguzzi A, Weissmann C (1994) Behavioral and anatomical deficits in mice homozygous for a modified beta-amyloid precursor protein gene. Cell 179(5):7557–7565

    Google Scholar 

  • Müller T, Concannon CG, Ward MW, Walsh CM, Tirniceriu AL, Tribl F, Kögel D, Prehn JH, Egensperger R (2007) Modulation of gene expression and cytoskeletal dynamics by the amyloid precursor protein intracellular domain (AICD). Mol Biol Cell 18(1):201–210

    Article  PubMed  CAS  Google Scholar 

  • Nakagawa K, Kitazume S, Oka R, Maruyama K, Saido TC, Sato Y, Endo T, Hashimoto Y (2006) Sialylation enhances the secretion of neurotoxic amyloid-beta peptides. J Neurochem 96(4):924–933

    Article  PubMed  CAS  Google Scholar 

  • Nikolaev A, McLaughlin T, O’Leary DD, Tessier-Lavigne M (2009) APP binds DR6 to trigger axon pruning and neuron death via distinct caspases. Nature 457(7232):981–989

    Article  PubMed  CAS  Google Scholar 

  • Pan D, Rubin GM (1997) Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis. Cell 90(2):271–280

    Article  PubMed  CAS  Google Scholar 

  • Reid PC, Urano Y, Kodama T, Hamakubo T (2007) Alzheimer’s disease: cholesterol, membrane rafts, isoprenoids and statins. J Cell Mol Med 11(3):383–392

    Article  PubMed  CAS  Google Scholar 

  • Robakis NK, Ramakrishna N, Wolfe G, Wisniewski HM (1987) Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides. Proc Natl Acad Sci USA 84(12):4190–4194

    Article  PubMed  CAS  Google Scholar 

  • Roberts SB, Ripellino JA, Ingalls KM, Robakis NK, Felsenstein KM (1994) Non-amyloidogenic cleavage of the beta-amyloid precursor protein by an integral membrane metalloendopeptidase. J Biol Chem 269(4):3111–3116

    PubMed  CAS  Google Scholar 

  • Rooke J, Pan D, Xu T, Rubin GM (1996) KUZ, a conserved metalloprotease-disintegrin protein with two roles in Drosophila neurogenesis. Science 273(5279):1227–1231

    Article  PubMed  CAS  Google Scholar 

  • Rosen DR, Martin-Morris L, Luo LQ, White K (1989) A Drosophila gene encoding a protein resembling the human beta-amyloid protein precursor. Proc Natl Acad Sci USA 86(7):2478–2482

    Article  PubMed  CAS  Google Scholar 

  • Selkoe DJ (2001) Alzheimer’s disease: genes, proteins, and therapy. Physiol Rev 81(2):741–766

    PubMed  CAS  Google Scholar 

  • Senechal Y, Larmet Y, Dev KK (2006) Unraveling in vivo functions of amyloid precursor protein: insights from knockout and knockdown studies. Neurodegener Dis 3(3):134–147

    Article  PubMed  CAS  Google Scholar 

  • Sinha S, Anderson JP, Barbour R, Basi GS, Caccavello R, Davis D, Doan M, Dovey HF, Frigon N, Hong J, Jacobson-Croak K, Jewett N, Keim P, Knops J, Lieberburg I, Power M, Tan H, Tatsuno G, Tung J, Schenk D, Seubert P, Suomensaari SM, Wang S, Walker D, Zhao J, McConlogue L, John V (1999) Purification and cloning of amyloid precursor protein beta-secretase from human brain. Nature 402(6761):537–540

    Google Scholar 

  • Soba P, Eggert S, Wagner K, Zentgraf H, Siehl K, Kreger S, Löwer A, Langer A, Merdes G, Paro R, Masters CL, Müller U, Kins S, Beyreuther K (2005) Homo- and heterodimerization of APP family members promotes intercellular adhesion. EMBO J 24(20):3624–3634

    Article  PubMed  CAS  Google Scholar 

  • Solans A, Estivill X, de La Luna S (2001) A new aspartyl protease on 21q22.3, BACE2, is highly similar to Alzheimer’s amyloid precursor protein beta-secretase. Cytogenet Cell Genet 89(3–4):177–184

    Google Scholar 

  • Sone M, Uchida A, Komatsu A, Suzuki E, Ibuki I, Asada M, Shiwaku H, Tamura T, Hoshino M, Okazawa H, Nabeshima Y (2009) Loss of yata, a novel gene regulating the subcellular localization of APPL, induces deterioration of neural tissues and lifespan shortening. PLoS ONE 4(2):e4466

    Article  PubMed  CAS  Google Scholar 

  • Stempfle D, Kanwar R, Loewer A, Fortini ME, Merdes G (2010) In vivo reconstitution of gamma-secretase in Drosophila results in substrate specificity. Mol Cell Biol 30(13):3165–3175

    Article  PubMed  CAS  Google Scholar 

  • Struhl G, Greenwald I (1999) Presenilin is required for activity and nuclear access of Notch in Drosophila. Nature 398(6727):522–525

    Article  PubMed  CAS  Google Scholar 

  • Tanaka S, Shiojiri S, Takahashi Y, Kitaguchi N, Ito H, Kameyama M, Kimura J, Nakamura S, Ueda K (1989) Tissue-specific expression of three types of beta-protein precursor mRNA: enhancement of protease inhibitor-harboring types in Alzheimer’s disease brain. Biochem Biophys Res Commun 165(3):1406–1414

    Google Scholar 

  • Tanzi RE, Gusella JF, Watkins PC, Bruns GA, St George-Hyslop P, Van Keuren ML, Patterson D, Pagan S, Kurnit DM, Neve RL (1987) Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the alzheimer locus. Science 235(4791):880–884

    Article  PubMed  CAS  Google Scholar 

  • Torroja L, Luo L, White K (1996) APPL, the Drosophila member of the APP-family, exhibits differential trafficking and processing in CNS neurons. J Neurosci 16(15):4638–4650

    Google Scholar 

  • Torroja L, Packard M, Gorczyca M, White K, Budnik V (1999a) The Drosophila beta-amyloid precursor protein homolog promotes synapse differentiation at the neuromuscular junction. J Neurosci 19(18):7793–7803

    PubMed  CAS  Google Scholar 

  • Torroja L, Chu H, Kotovsky I, White K (1999b) Neuronal overexpression of APPL, the Drosophila homologue of the amyloid precursor protein (APP), disrupts axonal transport. Curr Biol 9(9):489–492

    Article  PubMed  CAS  Google Scholar 

  • Tschäpe JA, Hammerschmied C, Mühlig-Versen M, Athenstaedt K, Daum G, Kretzschmar D (2002) The neurodegeneration mutant löchrig interferes with cholesterol homeostasis and APPL processing. EMBO J 21(23):6367–6376

    Article  PubMed  Google Scholar 

  • Tully T, Quinn WG (1985) Classical conditioning and retention in normal and mutant Drosophila melanogaster. J Comp Physiol A 157(2):263–277

    Article  PubMed  CAS  Google Scholar 

  • Turner PR, O’Connor K, Tate WP, Abraham WC (2003) Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog Neurobiol 70(1):1–32

    Article  PubMed  CAS  Google Scholar 

  • Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, Lile J, Jarosinski MA, Biere AL, Curran E, Burgess T, Louis JC, Collins F, Treanor J, Rogers G, Citron M (1999) Beta-secretase cleavage of alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286(5440):735–741

    Article  PubMed  CAS  Google Scholar 

  • Wolfe MS, Xia W, Ostaszewski BL, Diehl TS, Kimberly WT, Selkoe DJ (1999) Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature 398(6727):513–517

    Article  PubMed  CAS  Google Scholar 

  • Yan R, Bienkowski MJ, Shuck ME, Miao H, Tory MC, Pauley AM, Brashier JR, Stratman NC, Mathews WR, Buhl AE, Carter DB, Tomasselli AG, Parodi LA, Heinrikson RL, Gurney ME (1999) Membrane-anchored aspartyl protease with alzheimer’s disease beta-secretase activity. Nature 402(6761):533–537

    Article  PubMed  CAS  Google Scholar 

  • Ye Y, Lukinova N, Fortini ME (1999) Neurogenic phenotypes and altered Notch processing in Drosophila Presenilin mutants. Nature 398(6727):525–529

    Article  PubMed  CAS  Google Scholar 

  • Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song YQ, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang DS, Holmes E, Milman P, Liang Y, Zhang DM, Xu DH, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer LS, Sorbi S, Bruni A, Fraser P, St George-Hyslop P (2000) Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and βAPP processing. Nature 407(6800):48–54

    Article  PubMed  CAS  Google Scholar 

  • Zheng H, Jiang M, Trumbauer ME, Sirinathsinghji DJ, Hopkins R, Smith DW, Heavens RP, Dawson GR, Boyce S, Conner MW, Stevens KA, Slunt HH, Sisoda SS, Chen HY, Van der Ploeg LH (1995) beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell 81(4):525–531

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Zoologie III–Neurobiologie, Johannes Gutenberg-Universität Mainz, Colonel Kleinmann-Weg 2, 55099, Mainz, Germany

    Burkhard Poeck & Roland Strauss

  2. Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR, 97239, USA

    Doris Kretzschmar

Authors
  1. Burkhard Poeck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roland Strauss
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Doris Kretzschmar
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Doris Kretzschmar.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Poeck, B., Strauss, R. & Kretzschmar, D. Analysis of amyloid precursor protein function in Drosophila melanogaster . Exp Brain Res 217, 413–421 (2012). https://doi.org/10.1007/s00221-011-2860-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-011-2860-3

Keywords

Search

Navigation