pubmed-article:15644323 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:15644323 | lifeskim:mentions | umls-concept:C2753842 | lld:lifeskim |
pubmed-article:15644323 | lifeskim:mentions | umls-concept:C1704675 | lld:lifeskim |
pubmed-article:15644323 | lifeskim:mentions | umls-concept:C0599896 | lld:lifeskim |
pubmed-article:15644323 | lifeskim:mentions | umls-concept:C1314939 | lld:lifeskim |
pubmed-article:15644323 | lifeskim:mentions | umls-concept:C1880177 | lld:lifeskim |
pubmed-article:15644323 | lifeskim:mentions | umls-concept:C0441712 | lld:lifeskim |
pubmed-article:15644323 | pubmed:issue | 13 | lld:pubmed |
pubmed-article:15644323 | pubmed:dateCreated | 2005-3-28 | lld:pubmed |
pubmed-article:15644323 | pubmed:abstractText | Gamma-secretase cleaves type I transmembrane proteins, including beta-amyloid precursor protein and Notch, and requires the formation of a protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2 for its activity. Aph-1 is implicated in the stabilization of this complex, although its precise mechanistic role remains unknown. Substitution of the first glycine within the transmembrane GXXXG motif of Aph-1 causes a loss-of-function phenotype in Caenorhabditis elegans. Here, using an untranslated region-targeted RNA interference/rescue strategy in Drosophila Schneider 2 cells, we show that Aph-1 contributes to the assembly of the gamma-secretase complex by multiple mechanisms involving intermolecular and intramolecular interactions depending on or independent of the conserved glycines. Aph-1 binds to nicastrin forming an early subcomplex independent of the conserved glycines within the endoplasmic reticulum. Certain mutations in the conserved GXXXG motif affect the interaction of the Aph-1.nicastrin subcomplex with presenilin that mediates trafficking of the presenilin.Aph-1.nicastrin tripartite complex to the Golgi. The same mutations decrease the stability of Aph-1 polypeptides themselves, possibly by affecting intramolecular associations through the transmembrane domains. Our data suggest that the proper assembly of the Aph-1.nicastrin subcomplex with presenilin is the prerequisite for the trafficking as well as the enzymatic activity of the gamma-secretase complex and that Aph-1 functions as a stabilizing scaffold in the assembly of this complex. | lld:pubmed |
pubmed-article:15644323 | pubmed:language | eng | lld:pubmed |
pubmed-article:15644323 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15644323 | pubmed:citationSubset | IM | lld:pubmed |
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pubmed-article:15644323 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15644323 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15644323 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:15644323 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:15644323 | pubmed:month | Apr | lld:pubmed |
pubmed-article:15644323 | pubmed:issn | 0021-9258 | lld:pubmed |
pubmed-article:15644323 | pubmed:author | pubmed-author:IwatsuboTakes... | lld:pubmed |
pubmed-article:15644323 | pubmed:author | pubmed-author:MorohashiYuic... | lld:pubmed |
pubmed-article:15644323 | pubmed:author | pubmed-author:TakasugiNobum... | lld:pubmed |
pubmed-article:15644323 | pubmed:author | pubmed-author:TomitaTaisuke... | lld:pubmed |
pubmed-article:15644323 | pubmed:author | pubmed-author:Ui-TeiKumikoK | lld:pubmed |
pubmed-article:15644323 | pubmed:author | pubmed-author:SaigoKaoruK | lld:pubmed |
pubmed-article:15644323 | pubmed:author | pubmed-author:TsuruokaMakik... | lld:pubmed |
pubmed-article:15644323 | pubmed:author | pubmed-author:NiimuraManabu... | lld:pubmed |
pubmed-article:15644323 | pubmed:author | pubmed-author:IsooNorikoN | lld:pubmed |
pubmed-article:15644323 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:15644323 | pubmed:day | 1 | lld:pubmed |
pubmed-article:15644323 | pubmed:volume | 280 | lld:pubmed |
pubmed-article:15644323 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:15644323 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:15644323 | pubmed:pagination | 12967-75 | lld:pubmed |
pubmed-article:15644323 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
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pubmed-article:15644323 | pubmed:year | 2005 | lld:pubmed |
pubmed-article:15644323 | pubmed:articleTitle | Aph-1 contributes to the stabilization and trafficking of the gamma-secretase complex through mechanisms involving intermolecular and intramolecular interactions. | lld:pubmed |
pubmed-article:15644323 | pubmed:affiliation | Department of Neuropathology and Neuroscience, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan. | lld:pubmed |
pubmed-article:15644323 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:15644323 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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