Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Bae, Dong-Jun | - |
dc.contributor.author | Seo, Junyoung | - |
dc.contributor.author | Kim, Sang-Yeob | - |
dc.contributor.author | Park, Seung-Yoon | - |
dc.contributor.author | Yoo, Jae Do | - |
dc.contributor.author | Pyo, Jae-Hoon | - |
dc.contributor.author | Cho, Wonhwa | - |
dc.contributor.author | Cho, Je-Yoel | - |
dc.contributor.author | Kim, Soyoun | - |
dc.contributor.author | Kim, In-San | - |
dc.date.accessioned | 2024-01-19T19:03:07Z | - |
dc.date.available | 2024-01-19T19:03:07Z | - |
dc.date.created | 2021-09-05 | - |
dc.date.issued | 2019-10 | - |
dc.identifier.issn | 0167-4889 | - |
dc.identifier.uri | https://pubs.kist.re.kr/handle/201004/119497 | - |
dc.description.abstract | The 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.language | English | - |
dc.publisher | ELSEVIER | - |
dc.subject | CELL CORPSE CLEARANCE | - |
dc.subject | ACTIN CYTOSKELETON | - |
dc.subject | APOPTOTIC CELLS | - |
dc.subject | PHAGOCYTOSIS | - |
dc.subject | PROTEIN | - |
dc.subject | CDC42 | - |
dc.subject | PHOSPHATIDYLSERINE | - |
dc.subject | ACTIVATION | - |
dc.subject | ENGULFMENT | - |
dc.subject | RECEPTOR | - |
dc.title | ArhGAP12 plays dual roles in Stabilin-2 mediated efferocytosis: Regulates Rac1 basal activity and spatiotemporally turns off the Rac1 to orchestrate phagosome maturation | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.bbamcr.2019.07.003 | - |
dc.description.journalClass | 1 | - |
dc.identifier.bibliographicCitation | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, v.1866, no.10, pp.1595 - 1607 | - |
dc.citation.title | BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | - |
dc.citation.volume | 1866 | - |
dc.citation.number | 10 | - |
dc.citation.startPage | 1595 | - |
dc.citation.endPage | 1607 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.identifier.wosid | 000482498400008 | - |
dc.identifier.scopusid | 2-s2.0-85069178539 | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Cell Biology | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Cell Biology | - |
dc.type.docType | Article | - |
dc.subject.keywordPlus | CELL CORPSE CLEARANCE | - |
dc.subject.keywordPlus | ACTIN CYTOSKELETON | - |
dc.subject.keywordPlus | APOPTOTIC CELLS | - |
dc.subject.keywordPlus | PHAGOCYTOSIS | - |
dc.subject.keywordPlus | PROTEIN | - |
dc.subject.keywordPlus | CDC42 | - |
dc.subject.keywordPlus | PHOSPHATIDYLSERINE | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | ENGULFMENT | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordAuthor | ArhGAP12 | - |
dc.subject.keywordAuthor | Rac1 activity | - |
dc.subject.keywordAuthor | Efferocytosis | - |
dc.subject.keywordAuthor | Phosphatidylinositol-4,5-bisphosphate | - |
dc.subject.keywordAuthor | Phagosome maturation | - |
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