LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 윤혜진 | - |
dc.contributor.author | 박주현 | - |
dc.contributor.author | 호동환 | - |
dc.contributor.author | 김혜정 | - |
dc.contributor.author | 김시현 | - |
dc.contributor.author | 오학진 | - |
dc.contributor.author | 서혜명 | - |
dc.contributor.author | 장성호 | - |
dc.contributor.author | 설원기 | - |
dc.contributor.author | 가인화 | - |
dc.contributor.author | 손일홍 | - |
dc.date.accessioned | 2021-06-23T04:45:35Z | - |
dc.date.available | 2021-06-23T04:45:35Z | - |
dc.date.created | 2021-01-22 | - |
dc.date.issued | 2013-08 | - |
dc.identifier.issn | 1226-3613 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/29731 | - |
dc.description.abstract | Leucine-rich repeat kinase 2 (LRRK2) is a gene that, upon mutation, causes autosomal-dominant familial Parkinson’s disease (PD). Yeast two-hybrid screening revealed that Snapin, a SNAP-25 (synaptosomal-associated protein-25) interacting protein,interacts with LRRK2. An in vitro kinase assay exhibited that Snapin is phosphorylated by LRRK2. A glutathione-S-transferase (GST) pull-down assay showed that LRRK2 may interact with Snapin via its Ras-of-complex (ROC) and N-terminal domains,with no significant difference on interaction of Snapin with LRRK2 wild type (WT) or its pathogenic mutants. Further analysis by mutation study revealed that Threonine 117 of Snapin is one of the sites phosphorylated by LRRK2. Furthermore, a Snapin T117D phosphomimetic mutant decreased its interaction with SNAP-25 in the GST pull-down assay. SNAP-25 is a component of the SNARE (Soluble NSF Attachment protein REceptor) complex and is critical for the exocytosis of synaptic vesicles. Incubation of rat brain lysate with recombinant Snapin T117D, but not WT, protein caused decreased interaction of synaptotagmin with the SNARE complex based on a co-immunoprecipitation assay. We further found that LRRK2-dependent phosphorylation of Snapin in the hippocampal neurons resulted in a decrease in the number of readily releasable vesicles and the extent of exocytotic release. Combined, these data suggest that LRRK2 may regulate neurotransmitter release via control of Snapin function by inhibitory phosphorylation. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | 생화학분자생물학회 | - |
dc.title | LRRK2 phosphorylates Snapin and inhibits interaction of Snapin with SNAP-25 | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | 서혜명 | - |
dc.identifier.scopusid | 2-s2.0-84883034462 | - |
dc.identifier.wosid | 000328122800003 | - |
dc.identifier.bibliographicCitation | Experimental and Molecular Medicine, v.45, no.8, pp.1 - 11 | - |
dc.relation.isPartOf | Experimental and Molecular Medicine | - |
dc.citation.title | Experimental and Molecular Medicine | - |
dc.citation.volume | 45 | - |
dc.citation.number | 8 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 11 | - |
dc.type.rims | ART | - |
dc.identifier.kciid | ART001794869 | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Research & Experimental Medicine | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Medicine, Research & Experimental | - |
dc.subject.keywordPlus | DISEASE-ASSOCIATED MUTATIONS | - |
dc.subject.keywordPlus | VI ADENYLYL-CYCLASE | - |
dc.subject.keywordPlus | PARKINSONS-DISEASE | - |
dc.subject.keywordPlus | KINASE-ACTIVITY | - |
dc.subject.keywordPlus | DOPAMINERGIC-NEURONS | - |
dc.subject.keywordPlus | GTP-BINDING | - |
dc.subject.keywordPlus | IN-VITRO | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | DOMAIN | - |
dc.subject.keywordPlus | GENE | - |
dc.subject.keywordAuthor | kinase | - |
dc.subject.keywordAuthor | LRRK2 | - |
dc.subject.keywordAuthor | Snapin | - |
dc.subject.keywordAuthor | SNAP-25 | - |
dc.subject.keywordAuthor | SNARE vesicle | - |
dc.subject.keywordAuthor | synaptotagmin | - |
dc.identifier.url | https://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART001794869 | - |
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