{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:39:04Z","timestamp":1792715944693,"version":"4.5.0"},"reference-count":10,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2010,5,22]],"date-time":"2010-05-22T00:00:00Z","timestamp":1274486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2010,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Fabry disease is an X\u2010linked lysosomal storage disorder that leads to abnormal accumulation of glycosphingolipids due to a deficiency of alpha\u2010galactosidase A (AGAL). The consequences of these alterations on the targeting of membrane proteins are poorly understood. Glycosphingolipids are enriched in Triton\u2010X\u2010100\u2010 resistant lipid rafts [detergent\u2010resistant membranes (DRMs)] and play an important role in the transport of several membrane\u2010associated proteins. Here, we show that In fibroblasts of patients suffering from Fabry disease, the colocalization of AGAL with the lysosomal marker LAMP2 is decreased compared with wild\u2010type fibroblasts concomitant with a reduced transport of AGAL to lysosomes. Furthermore, overall composition of membrane lipids in the patients\u2019 fibroblasts as well as in DRMs reveals a substantial increase in the concentration of glycolipids and a slight reduction of phosphatidylethanolamine (PE). The altered glycolipid composition in Fabry fibroblasts is associated with an intracellular accumulation and impaired trafficking of the Triton\u2010X\u2010100 DRM\u2010associated membrane glycoprotein dipeptidyl peptidase IV (DPPIV) in transfected Fabry cells, whereas no effect could be observed on the targeting of aminopeptidase N (ApN) that is not associated with this type of DRM. We propose that changes in the lipid composition of cell membranes in Fabry disease disturb the ordered Triton X\u2010100 DRMs and have implications on the trafficking and sorting of DRM\u2010associated proteins and the overall protein\u2013lipid interaction at the cell membrane. Possible consequences could be altered signalling at the cell surface triggered by DRM\u2010associated proteins, with implications on gene regulation and subsequent protein expression.<\/jats:p>","DOI":"10.1007\/s10545-010-9114-6","type":"journal-article","created":{"date-parts":[[2010,5,21]],"date-time":"2010-05-21T07:12:11Z","timestamp":1274425931000},"page":"445-449","source":"Crossref","is-referenced-by-count":17,"title":["A modified lipid composition in Fabry disease leads to an intracellular block of the detergent\u2010resistant membrane\u2010associated dipeptidyl peptidase IV"],"prefix":"10.1002","volume":"33","author":[{"given":"Katia","family":"Maalouf","sequence":"first","affiliation":[{"name":"Department of Physiological Chemistry University of Veterinary Medicine Buenteweg 17 Hannover 30559 Germany"},{"name":"Department of Pediatrics Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry University of Veterinary Medicine Buenteweg 17 Hannover 30559 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Rizk","sequence":"additional","affiliation":[{"name":"Department of Natural Sciences Lebanese\u2010American University Beirut Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Graham","family":"Brogden","sequence":"additional","affiliation":[{"name":"Fish Disease Research Unit, Centre of Infectious Diseases University of Veterinary Medicine Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Keiser","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry University of Veterinary Medicine Buenteweg 17 Hannover 30559 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anibh","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan Y.","family":"Naim","sequence":"additional","affiliation":[{"name":"Department of Physiological Chemistry University of Veterinary Medicine Buenteweg 17 Hannover 30559 Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2010,5,22]]},"reference":[{"key":"e_1_2_4_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109357200"},{"key":"e_1_2_4_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505924200"},{"key":"e_1_2_4_4_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511364200"},{"key":"e_1_2_4_5_1","doi-asserted-by":"publisher","DOI":"10.1139\/y59-099"},{"key":"e_1_2_4_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2002.tb03102.x"},{"key":"e_1_2_4_7_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.21.122303.120013"},{"key":"e_1_2_4_8_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R500015200"},{"key":"e_1_2_4_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04399"},{"key":"e_1_2_4_10_1","volume-title":"The metabolic and molecular bases of inherited disease","author":"Scriver CR","year":"2001"},{"key":"e_1_2_4_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10212"}],"container-title":["Journal of Inherited Metabolic Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-010-9114-6","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1007\/s10545-010-9114-6","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1007\/s10545-010-9114-6","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T13:33:03Z","timestamp":1694784783000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1007\/s10545-010-9114-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5,22]]},"references-count":10,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2010,8]]}},"alternative-id":["10.1007\/s10545-010-9114-6"],"URL":"https:\/\/doi.org\/10.1007\/s10545-010-9114-6","archive":["Portico"],"relation":{},"ISSN":["0141-8955","1573-2665"],"issn-type":[{"value":"0141-8955","type":"print"},{"value":"1573-2665","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,5,22]]}}}