{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T22:08:24Z","timestamp":1789855704030,"version":"4.0.1"},"reference-count":35,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,2,24]],"date-time":"2015-02-24T00:00:00Z","timestamp":1424736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Traffic"],"published-print":{"date-parts":[[2015,5]]},"abstract":"The triggering receptor expressed on myeloid cells 2 (TREM2<\/jats:styled-content>) is an immune\u2010modulatory receptor involved in phagocytosis and inflammation. Mutations of Q33X<\/jats:styled-content>, Y38C<\/jats:styled-content> and T66M<\/jats:styled-content> cause Nasu\u2010Hakola disease (NHD<\/jats:styled-content>) which is characterized by early onset of dementia and bone cysts. A recent, genome\u2010wide association study also revealed that single nucleotide polymorphism of TREM2<\/jats:styled-content>, such as R47H<\/jats:styled-content>, increased the risk of Alzheimer's disease (AD<\/jats:styled-content>) similar to ApoE4<\/jats:styled-content>. However, how these mutations affect the trafficking of TREM2<\/jats:styled-content>, which may affect the normal functions of TREM2<\/jats:styled-content>, was not known. In this study, we show that TREM2<\/jats:styled-content> with NHD<\/jats:styled-content> mutations are impaired in the glycosylation with complex oligosaccharides in the Golgi apparatus, in the trafficking to plasma membrane and further processing by \u03b3\u2010secretase. Although R47H<\/jats:styled-content> mutation in AD<\/jats:styled-content> affected the glycosylation and normal trafficking of TREM2<\/jats:styled-content> less, the detailed pattern of glycosylated TREM2<\/jats:styled-content> differs from that of the wild type, thus suggesting that precise regulation of TREM2<\/jats:styled-content> glycosylation is impaired when arginine at 47 is mutated to histidine. Our results suggest that the impaired glycosylation and trafficking of TREM2<\/jats:styled-content> from endoplasmic reticulum\/Golgi to plasma membrane by mutations may inhibit its normal functions in the plasma membrane, which may contribute to the disease.<\/jats:p><\/jats:p>","DOI":"10.1111\/tra.12264","type":"journal-article","created":{"date-parts":[[2015,1,23]],"date-time":"2015-01-23T13:27:58Z","timestamp":1422019678000},"page":"510-518","source":"Crossref","is-referenced-by-count":82,"title":["Disease\u2010Associated Mutations of TREM2<\/scp> Alter the Processing of N\u2010Linked Oligosaccharides in the Golgi Apparatus"],"prefix":"10.1111","volume":"16","author":[{"given":"Ji\u2010Seon","family":"Park","sequence":"first","affiliation":[{"name":"Alzheimer's Disease Experts Lab (ADEL), Asan Medical Center University of Ulsan College of Medicine Seoul Republic of Korea"},{"name":"Department of Brain Science University of Ulsan College of Medicine Seoul Republic of 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Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min\u2010Ji","family":"Kang","sequence":"additional","affiliation":[{"name":"Bio\u2010Medical Institute of Technology (BMIT) University of Ulsan College of Medicine Seoul Republic of Korea"},{"name":"Cell Dysfunction Research Center (CDRC) University of Ulsan College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang\u2010Wook","family":"Kang","sequence":"additional","affiliation":[{"name":"Bio\u2010Medical Institute of Technology (BMIT) University of Ulsan College of Medicine Seoul Republic of Korea"},{"name":"Cell Dysfunction Research Center (CDRC) University of Ulsan College of Medicine Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong\u2010Hou","family":"Kim","sequence":"additional","affiliation":[{"name":"Alzheimer's Disease Experts Lab (ADEL), Asan Medical Center University of Ulsan College of Medicine Seoul 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