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dc.contributor.authorBae, Dong-Jun-
dc.contributor.authorSeo, Junyoung-
dc.contributor.authorKim, Sang-Yeob-
dc.contributor.authorPark, Seung-Yoon-
dc.contributor.authorYoo, Jae Do-
dc.contributor.authorPyo, Jae-Hoon-
dc.contributor.authorCho, Wonhwa-
dc.contributor.authorCho, Je-Yoel-
dc.contributor.authorKim, Soyoun-
dc.contributor.authorKim, In-San-
dc.date.accessioned2024-01-19T19:03:07Z-
dc.date.available2024-01-19T19:03:07Z-
dc.date.created2021-09-05-
dc.date.issued2019-10-
dc.identifier.issn0167-4889-
dc.identifier.urihttps://pubs.kist.re.kr/handle/201004/119497-
dc.description.abstractThe rapid and precise clearance of apoptotic cells (efferocytosis) involves a series of phagocytic processes through which apoptotic cells are recognized, engulfed, and degraded within phagocytes. The Rho-family GTPases critically rearrange the cytoskeleton for these phagocytic processes, but we know little about the mechanisms by which regulatory proteins control the spatiotemporal activities of the Rho-family GTPases. Here, we identify ArhGAP12 as a functional GTPase-activating protein (GAP) of Rac1 during Stabilin-2 mediated efferocytosis. ArhGAP12 constitutively forms a complex with the phosphatidylserine receptor, Stabilin-2, via direct interaction with the downstream protein, GULP, but is released from the complex when Stabilin-2 interacts with apoptotic cells. When the phagocytic cup is closed and the apoptotic cell is surrounded by the phagosomal membrane, ArhGAP12 localizes to the phagocytic cup via a specific interaction with phosphatidylinositol-4,5-bisphosphate, which is transiently biosynthesized in the phagocytic cup. Down-regulation of ArhGAP12 results in sustained Rac1 activity, arrangement of F-actin, and delayed phagosome-lysosome fusion. Our results collectively suggest that ArhGAP12 carries dual roles in Stabilin-2 mediated efferocytosis: it binds to GULP/Stabilin-2 and switches off Rac1 basal activity and switches on the Rac1 by releasing itself from the complex. In addition, the spatiotemporal membrane targeting of ArhGAP12 inactivates Rac1 in a time-specific and spatially coordinated manner to orchestrate phagosome maturation. This may shed light on how other RhoGAPs spatiotemporally inactivate Rac or Cdc42 during phagocytosis by various cells, in different circumstances.-
dc.languageEnglish-
dc.publisherELSEVIER-
dc.subjectCELL CORPSE CLEARANCE-
dc.subjectACTIN CYTOSKELETON-
dc.subjectAPOPTOTIC CELLS-
dc.subjectPHAGOCYTOSIS-
dc.subjectPROTEIN-
dc.subjectCDC42-
dc.subjectPHOSPHATIDYLSERINE-
dc.subjectACTIVATION-
dc.subjectENGULFMENT-
dc.subjectRECEPTOR-
dc.titleArhGAP12 plays dual roles in Stabilin-2 mediated efferocytosis: Regulates Rac1 basal activity and spatiotemporally turns off the Rac1 to orchestrate phagosome maturation-
dc.typeArticle-
dc.identifier.doi10.1016/j.bbamcr.2019.07.003-
dc.description.journalClass1-
dc.identifier.bibliographicCitationBIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v.1866, no.10, pp.1595 - 1607-
dc.citation.titleBIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH-
dc.citation.volume1866-
dc.citation.number10-
dc.citation.startPage1595-
dc.citation.endPage1607-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.identifier.wosid000482498400008-
dc.identifier.scopusid2-s2.0-85069178539-
dc.relation.journalWebOfScienceCategoryBiochemistry & Molecular Biology-
dc.relation.journalWebOfScienceCategoryCell Biology-
dc.relation.journalResearchAreaBiochemistry & Molecular Biology-
dc.relation.journalResearchAreaCell Biology-
dc.type.docTypeArticle-
dc.subject.keywordPlusCELL CORPSE CLEARANCE-
dc.subject.keywordPlusACTIN CYTOSKELETON-
dc.subject.keywordPlusAPOPTOTIC CELLS-
dc.subject.keywordPlusPHAGOCYTOSIS-
dc.subject.keywordPlusPROTEIN-
dc.subject.keywordPlusCDC42-
dc.subject.keywordPlusPHOSPHATIDYLSERINE-
dc.subject.keywordPlusACTIVATION-
dc.subject.keywordPlusENGULFMENT-
dc.subject.keywordPlusRECEPTOR-
dc.subject.keywordAuthorArhGAP12-
dc.subject.keywordAuthorRac1 activity-
dc.subject.keywordAuthorEfferocytosis-
dc.subject.keywordAuthorPhosphatidylinositol-4,5-bisphosphate-
dc.subject.keywordAuthorPhagosome maturation-
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