K. Akasaka-Manya, Masaki Kawamura, H. Tsumoto, Yuko Saito, Y. Tachida, S. Kitazume, H. Hatsuta, Y. Miura, S. Hisanaga, S. Murayama, Y. Hashimoto, H. Manya, T. Endo
{"title":"Excess APP O-glycosylation by GalNAc-T6 decreases A&bgr; production","authors":"K. Akasaka-Manya, Masaki Kawamura, H. Tsumoto, Yuko Saito, Y. Tachida, S. Kitazume, H. Hatsuta, Y. Miura, S. Hisanaga, S. Murayama, Y. Hashimoto, H. Manya, T. Endo","doi":"10.1093/jb/mvw056","DOIUrl":null,"url":null,"abstract":"Alterations of the structure and/or amount of glycans present on proteins are associated with many diseases. We previously demonstrated that changes in N-glycans alter A&bgr; production. In the present study, we focused on the relationship between Alzheimer’s disease (AD) and O-glycan, another type of glycan. The UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family functions in the first step of mucin-type O-glycan synthesis. Analysis of the expression of GalNAc-Ts in the human brain using real-time PCR revealed that the expression of several GalNAc-Ts was altered with sporadic AD progression. Three of these GalNAc-Ts (GalNAc-T1, GalNAc-T4 and GalNAc-T6) were transfected into HEK293T cells to examine their impact on A&bgr; production. Transfection of GalNAc-T6 significantly reduced both A&bgr;1-40 and A&bgr;1-42 generation, but GalNAc-T1 and GalNAc-T4 only reduced A&bgr;1-40 generation. Although these three GalNAc-Ts exhibited enzymatic activities on soluble amyloid precursor protein (APP), the GalNAc transferase activity of GalNAc-T6 to APP was most prominent. The expression of &agr;-secretase and &bgr;-secretase was slightly altered in the transfected cells, but the activities of &agr;-secretase and &bgr;-secretase were not significantly altered. These data suggest that excess O-glycosylation on APP by GalNAc-T6 inhibits A&bgr; production.","PeriodicalId":22605,"journal":{"name":"The Journal of Biochemistry","volume":"1 1","pages":"99–111"},"PeriodicalIF":0.0000,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"30","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Biochemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/jb/mvw056","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 30
Abstract
Alterations of the structure and/or amount of glycans present on proteins are associated with many diseases. We previously demonstrated that changes in N-glycans alter A&bgr; production. In the present study, we focused on the relationship between Alzheimer’s disease (AD) and O-glycan, another type of glycan. The UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T) family functions in the first step of mucin-type O-glycan synthesis. Analysis of the expression of GalNAc-Ts in the human brain using real-time PCR revealed that the expression of several GalNAc-Ts was altered with sporadic AD progression. Three of these GalNAc-Ts (GalNAc-T1, GalNAc-T4 and GalNAc-T6) were transfected into HEK293T cells to examine their impact on A&bgr; production. Transfection of GalNAc-T6 significantly reduced both A&bgr;1-40 and A&bgr;1-42 generation, but GalNAc-T1 and GalNAc-T4 only reduced A&bgr;1-40 generation. Although these three GalNAc-Ts exhibited enzymatic activities on soluble amyloid precursor protein (APP), the GalNAc transferase activity of GalNAc-T6 to APP was most prominent. The expression of &agr;-secretase and &bgr;-secretase was slightly altered in the transfected cells, but the activities of &agr;-secretase and &bgr;-secretase were not significantly altered. These data suggest that excess O-glycosylation on APP by GalNAc-T6 inhibits A&bgr; production.