Cited 8 times in
Adherens junctions organize size-selective proteolytic hotspots critical for Notch signalling
DC Field | Value | Language |
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dc.contributor.author | 김형범 | - |
dc.date.accessioned | 2023-06-02T00:39:43Z | - |
dc.date.available | 2023-06-02T00:39:43Z | - |
dc.date.issued | 2022-12 | - |
dc.identifier.issn | 1465-7392 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/194336 | - |
dc.description.abstract | Adherens junctions (AJs) create spatially, chemically and mechanically discrete microdomains at cellular interfaces. Here, using a mechanogenetic platform that generates artificial AJs with controlled protein localization, clustering and mechanical loading, we find that AJs also organize proteolytic hotspots for γ-secretase with a spatially regulated substrate selectivity that is critical in the processing of Notch and other transmembrane proteins. Membrane microdomains outside of AJs exclusively organize Notch ligand-receptor engagement (LRE microdomains) to initiate receptor activation. Conversely, membrane microdomains within AJs exclusively serve to coordinate regulated intramembrane proteolysis (RIP microdomains). They do so by concentrating γ-secretase and primed receptors while excluding full-length Notch. AJs induce these functionally distinct microdomains by means of lipid-dependent γ-secretase recruitment and size-dependent protein segregation. By excluding full-length Notch from RIP microdomains, AJs prevent inappropriate enzyme-substrate interactions and suppress spurious Notch activation. Ligand-induced ectodomain shedding eliminates size-dependent segregation, releasing Notch to translocate into AJs for processing by γ-secretase. This mechanism directs radial differentiation of ventricular zone-neural progenitor cells in vivo and more broadly regulates the proteolysis of other large cell-surface receptors such as amyloid precursor protein. These findings suggest an unprecedented role of AJs in creating size-selective spatial switches that choreograph γ-secretase processing of multiple transmembrane proteins regulating development, homeostasis and disease. | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Macmillan Magazines Ltd. | - |
dc.relation.isPartOf | NATURE CELL BIOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Amyloid Precursor Protein Secretases* / genetics | - |
dc.subject.MESH | Ligands | - |
dc.title | Adherens junctions organize size-selective proteolytic hotspots critical for Notch signalling | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pharmacology (약리학교실) | - |
dc.contributor.googleauthor | Minsuk Kwak | - |
dc.contributor.googleauthor | Kaden M Southard | - |
dc.contributor.googleauthor | Woon Ryoung Kim | - |
dc.contributor.googleauthor | Annie Lin | - |
dc.contributor.googleauthor | Nam Hyeong Kim | - |
dc.contributor.googleauthor | Ramu Gopalappa | - |
dc.contributor.googleauthor | Hyun Jung Lee | - |
dc.contributor.googleauthor | Minji An | - |
dc.contributor.googleauthor | Seo Hyun Choi | - |
dc.contributor.googleauthor | Yunmin Jung | - |
dc.contributor.googleauthor | Kunwoo Noh | - |
dc.contributor.googleauthor | Justin Farlow | - |
dc.contributor.googleauthor | Anastasios Georgakopoulos | - |
dc.contributor.googleauthor | Nikolaos K Robakis | - |
dc.contributor.googleauthor | Min K Kang | - |
dc.contributor.googleauthor | Matthew L Kutys | - |
dc.contributor.googleauthor | Daeha Seo | - |
dc.contributor.googleauthor | Hyongbum Henry Kim | - |
dc.contributor.googleauthor | Yong Ho Kim | - |
dc.contributor.googleauthor | Jinwoo Cheon | - |
dc.contributor.googleauthor | Zev J Gartner | - |
dc.contributor.googleauthor | Young-Wook Jun | - |
dc.identifier.doi | 10.1038/s41556-022-01031-6 | - |
dc.contributor.localId | A01148 | - |
dc.relation.journalcode | J02291 | - |
dc.identifier.eissn | 1476-4679 | - |
dc.identifier.pmid | 36456828 | - |
dc.identifier.url | https://www.nature.com/articles/s41556-022-01031-6 | - |
dc.contributor.alternativeName | Kim, Hyongbum | - |
dc.contributor.affiliatedAuthor | 김형범 | - |
dc.citation.volume | 24 | - |
dc.citation.number | 12 | - |
dc.citation.startPage | 1739 | - |
dc.citation.endPage | 1753 | - |
dc.identifier.bibliographicCitation | NATURE CELL BIOLOGY, Vol.24(12) : 1739-1753, 2022-12 | - |
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