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Tryptophan-dependent and -independent secretions of tryptophanyl- tRNA synthetase mediate innate inflammatory responses

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dc.date.accessioned2024-05-31T06:17:46Z-
dc.date.available2024-05-31T06:17:46Z-
dc.date.issued2023-01-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/199694-
dc.description.abstractWhile cytoplasmic tryptophanyl-tRNA synthetase (WARS1) ligates tryptophan (Trp) to its cognate tRNAs for protein synthesis, it also plays a role as an innate immune activator in extracellular space. However, its secretion mechanism remains elusive. Here, we report that in response to stimuli, WARS1 can be secreted via two distinct pathways: via Trp-dependent secretion of naked protein and via Trp-independent plasma-membrane-derived vesicles (PMVs). In the direct pathway, Trp binding to WARS1 induces a "closed" conformation, generating a hydrophobic surface and basic pocket. The Trp-bound WARS1 then binds stable phosphatidylinositol (4,5)-biphosphate and inner plasma membrane leaflet, passing across the membrane. In the PMV-mediated secretion, WARS1 recruits calpain 2, which is activated by calcium. WARS1 released from PMVs induces inflammatory responses in vivo. These results provide insights into the secretion mechanisms of WARS1 and improve our understanding of how WARS1 is involved in the control of local and systemic inflammation upon infection.-
dc.description.statementOfResponsibilityopen-
dc.languageEnglish-
dc.publisherCell Press-
dc.relation.isPartOfCELL REPORTS-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHHumans-
dc.subject.MESHInflammation-
dc.subject.MESHTryptophan / metabolism-
dc.subject.MESHTryptophan-tRNA Ligase* / genetics-
dc.titleTryptophan-dependent and -independent secretions of tryptophanyl- tRNA synthetase mediate innate inflammatory responses-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentOthers-
dc.contributor.googleauthorTram Thuy Thuy Nguyen-
dc.contributor.googleauthorYun Hui Choi-
dc.contributor.googleauthorWon-Kyu Lee-
dc.contributor.googleauthorYeounjung Ji-
dc.contributor.googleauthorEunho Chun-
dc.contributor.googleauthorYi Hyo Kim-
dc.contributor.googleauthorJoo-Eun Lee-
dc.contributor.googleauthorHyun Suk Jung-
dc.contributor.googleauthorJi Hun Suh-
dc.contributor.googleauthorSunghoon Kim-
dc.contributor.googleauthorMirim Jin-
dc.identifier.doi10.1016/j.celrep.2022.111905-
dc.relation.journalcodeJ00488-
dc.identifier.eissn2211-1247-
dc.identifier.pmid36640342-
dc.subject.keywordCP: Immunology-
dc.subject.keywordCP: Molecular biology-
dc.subject.keywordcalpain 2-
dc.subject.keywordinnate immune response-
dc.subject.keywordphosphatidylinositol (4,5)-biphosphate-
dc.subject.keywordplasma membrane-derived vesicles-
dc.subject.keywordtryptophan-
dc.subject.keywordtryptophanyl-tRNA synthetase-
dc.citation.volume42-
dc.citation.number1-
dc.citation.startPage111905-
dc.identifier.bibliographicCitationCELL REPORTS, Vol.42(1) : 111905, 2023-01-
Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 1. Journal Papers

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