{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363670321190658432.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1242/jcs.015255"}},{"identifier":{"@type":"URI","@value":"http://journals.biologists.com/jcs/article-pdf/121/4/413/1373465/413.pdf"}}],"dc:title":[{"@value":"Building γ-secretase – the bits and pieces"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>γ-Secretase is a promiscuous aspartyl protease responsible for the final intramembrane cleavage of various type I transmembrane proteins after their large ectodomains are shed. The vast functional diversity of its substrates, which are involved in cell fate decisions, adhesion, neurite outgrowth and synapse formation, highlights the important role γ-secretase plays in development and neurogenesis. The most renowned substrates are the amyloid precursor protein and Notch, from which γ-secretase liberates amyloid β peptides and induces downstream signalling, respectively. γ-Secretase is a multiprotein complex containing presenilin (which harbours the catalytic site), nicastrin, APH1 and PEN2. Its assembly occurs under tight control of ER-Golgi recycling regulators, which allows defined quantities of complexes to reach post-Golgi compartments, where γ-secretase activity is regulated by multiple other factors. 3D-EM rendering reveals a complex with a translucent inner space, suggesting the presence of a water-filled cavity required for intramembrane proteolysis. Despite huge efforts, we are now only beginning to unravel the assembly, stoichiometry, activation and subcellular location of γ-secretase.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1383670321190658432","@type":"Researcher","foaf:name":[{"@value":"Dragana Spasic"}],"jpcoar:affiliationName":[{"@value":"Laboratory for Membrane Trafficking, Center for Human Genetics (KULeuven) and Department of Molecular and Developmental Genetics (VIB), O&N1, Rm. 9.696, Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670321190658433","@type":"Researcher","foaf:name":[{"@value":"Wim Annaert"}],"jpcoar:affiliationName":[{"@value":"Laboratory for Membrane Trafficking, Center for Human Genetics (KULeuven) and Department of Molecular and Developmental Genetics (VIB), O&N1, Rm. 9.696, Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"14779137"},{"@type":"PISSN","@value":"00219533"}],"prism:publicationName":[{"@value":"Journal of Cell Science"}],"dc:publisher":[{"@value":"The Company of Biologists"}],"prism:publicationDate":"2008-02-15","prism:volume":"121","prism:number":"4","prism:startingPage":"413","prism:endingPage":"420"},"reviewed":"false","url":[{"@id":"http://journals.biologists.com/jcs/article-pdf/121/4/413/1373465/413.pdf"}],"createdAt":"2008-02-06","modifiedAt":"2024-02-22","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360290617662998016","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"High temperature promotes amyloid β-protein production and γ-secretase complex formation via Hsp90"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848658909173120","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"The Ubiquitin Ligase Synoviolin Up-regulates Amyloid β Production by Targeting a Negative Regulator of γ-Secretase, Rer1, for Degradation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848660713299200","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Alanine substitutions in the <scp>GXXXG</scp> motif alter C99 cleavage by γ‐secretase but not its dimerization"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1242/jcs.015255"},{"@type":"CROSSREF","@value":"10.1074/jbc.ra120.013845_references_DOI_9OfqCeQJEZZ8eXMSbNjKgfoqxMz"},{"@type":"CROSSREF","@value":"10.1074/jbc.m112.365296_references_DOI_9OfqCeQJEZZ8eXMSbNjKgfoqxMz"},{"@type":"CROSSREF","@value":"10.1111/jnc.13942_references_DOI_9OfqCeQJEZZ8eXMSbNjKgfoqxMz"}]}