{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T22:29:38Z","timestamp":1787005778933,"version":"build-2736575974"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1998,11,10]]},"abstract":"<jats:p>\n                    The importance of the amyloid precursor protein (APP) in the pathogenesis of Alzheimer\u2019s disease (AD) became apparent through the identification of distinct mutations in the APP gene, causing early onset familial AD with the accumulation of a 4-kDa peptide fragment (\u03b2A4) in amyloid plaques and vascular deposits. However, the physiological role of APP is still unclear. In this work,\n                    <jats:italic>Drosophila melanogaster<\/jats:italic>\n                    is used as a model system to analyze the function of APP by expressing wild-type and various mutant forms of human APP in fly tissue culture cells as well as in transgenic fly lines. After expression of full-length APP forms, secretion of APP but not of \u03b2A4 was observed in both systems. By using SPA4CT, a short APP form in which the signal peptide was fused directly to the \u03b2A4 region, transmembrane domain, and cytoplasmic tail, we observed \u03b2A4 release in flies and fly-tissue culture cells. Consequently, we showed a \u03b3-secretase activity in flies. Interestingly, transgenic flies expressing full-length forms of APP have a blistered-wing phenotype. As the wing is composed of interacting dorsal and ventral epithelial cell layers, this phenotype suggests that human APP expression interferes with cell adhesion\/signaling pathways in\n                    <jats:italic>Drosophila<\/jats:italic>\n                    , independently of \u03b2A4 generation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.95.23.13703","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:40:11Z","timestamp":1027680011000},"page":"13703-13708","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":125,"title":["Transgenic\n                    <i>Drosophila<\/i>\n                    expressing human amyloid precursor protein show \u03b3-secretase activity and a blistered-wing phenotype"],"prefix":"10.1073","volume":"95","author":[{"given":"Anke","family":"Fossgreen","sequence":"first","affiliation":[{"name":"Center for Molecular Biology, University of Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany; 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and Department of Pathology, University of Melbourne, Parkville, Victoria 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Beyreuther","sequence":"additional","affiliation":[{"name":"Center for Molecular Biology, University of Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany; and Department of Pathology, University of Melbourne, Parkville, Victoria 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Paro","sequence":"additional","affiliation":[{"name":"Center for Molecular Biology, University of Heidelberg, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany; and Department of Pathology, University of Melbourne, Parkville, Victoria 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1998,11,10]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/325733a0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)36778-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.22.10758"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0993-95"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1997.0354a.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.31.18295"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.24.12045"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.7.2478"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90024-8"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90073-X"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/373523a0"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.274.5284.99"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.52.30853"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90096-2"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0896-6273(92)90228-6"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.118.2.401"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0892-345"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(92)80730-5"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00907.x"},{"key":"e_1_3_3_20_2","first-page":"353","volume":"27","author":"Schneider I","year":"1972","unstructured":"I Schneider J Embryol Exp Morph 27, 353\u2013365 (1972).","journal-title":"J Embryol Exp Morph"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90341-3"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(89)90177-3"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.37.22908"},{"key":"e_1_3_3_24_2","first-page":"121","volume":"2","author":"Kim K","year":"1988","unstructured":"K Kim, D L Miller, M-C Chen, V J Sapienza, C Bai, I Grundke-Iqbal, J R Currie, H M Wiesniewski Neurosci Res Commun 2, 121\u2013130 (1988).","journal-title":"Neurosci Res Commun"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-03-00899.1996"},{"key":"e_1_3_3_26_2","first-page":"47","volume":"6","author":"Luckow V A","year":"1988","unstructured":"V A Luckow, M D Summers Bio\/Technology 6, 47\u201355 (1988).","journal-title":"Bio\/Technology"},{"key":"e_1_3_3_27_2","first-page":"843","volume-title":"The Development of Drosophila melanogaster","author":"Fristrom D","year":"1993","unstructured":"D Fristrom, J W Fristrom The Development of Drosophila melanogaster, eds M Bate, A M Arias (Cold Spring Harbor Lab. 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