MST1-dependent vesicle trafficking regulates neutrophil transmigration through the vascular basement membrane

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dc.contributor.authorKurz, Angela R. M.ko
dc.contributor.authorPruenster, Monikako
dc.contributor.authorRohwedder, Inako
dc.contributor.authorRamadass, Mahalakshmiko
dc.contributor.authorSchaefer, Kerstinko
dc.contributor.authorHarrison, Uteko
dc.contributor.authorGouveia, Gabrielko
dc.contributor.authorNussbaum, Claudiako
dc.contributor.authorImmler, Rolandko
dc.contributor.authorWiessner, Johannes R.ko
dc.contributor.authorMargraf, Andreasko
dc.contributor.authorLim, Dae-Sikko
dc.contributor.authorWalzog, Barbarako
dc.contributor.authorDietzel, Steffenko
dc.contributor.authorMoser, Markusko
dc.contributor.authorKlein, Christophko
dc.contributor.authorVestweber, Dietmarko
dc.contributor.authorHaas, Rainerko
dc.contributor.authorCatz, Sergio D.ko
dc.contributor.authorSperandio, Markusko
dc.date.accessioned2016-12-01T07:59:26Z-
dc.date.available2016-12-01T07:59:26Z-
dc.date.created2016-11-28-
dc.date.created2016-11-28-
dc.date.issued2016-11-
dc.identifier.citationJOURNAL OF CLINICAL INVESTIGATION, v.126, no.11, pp.4125 - 4139-
dc.identifier.issn0021-9738-
dc.identifier.urihttp://hdl.handle.net/10203/214595-
dc.description.abstractNeutrophils need to penetrate the perivascular basement membrane for successful extravasation into inflamed tissue, but this process is incompletely understood. Recent findings have associated mammalian sterile 20-like Kinase 1 (MST1) loss of function with a human primary immunodeficiency disorder, suggesting that MST1 may be involved in immune cell migration. Here, we have shown that MST1 is a critical regulator of neutrophil extravasation during inflammation. Mst1-deficient (Mst1(-/-)) neutrophils were unable to migrate into inflamed murine cremaster muscle venules, instead persisting between the endothelium and the basement membrane. Mst1(-/-) neutrophils also failed to extravasate from gastric submucosal vessels in a murine model of Helicobacter pylori infection. Mechanistically, we observed defective translocation of VLA-3, VLA-6, and neutrophil elastase from intracellular vesicles to the surface of Mst1(-/-) neutrophils, indicating that MST1 is required for this crucial step in neutrophil transmigration. Furthermore, we found that MST1 associates with the Rab27 effector protein synaptotagmin-like protein 1 (JFC1, encoded by Sytl1 in mice), but not Munc13-4, thereby regulating the trafficking of Rab27-positive vesicles to the cellular membrane. Together, these findings highlight a role for MST1 in vesicle trafficking and extravasation in neutrophils, providing an additional mechanistic explanation for the severe immune defect observed in patients with MST1 deficiency-
dc.languageEnglish-
dc.publisherAMER SOC CLINICAL INVESTIGATION INC-
dc.subjectIN-VIVO-
dc.subjectLEUKOCYTE MIGRATION-
dc.subjectTRANSENDOTHELIAL MIGRATION-
dc.subjectLYMPHOCYTE TRAFFICKING-
dc.subjectEXTRACELLULAR-MATRIX-
dc.subjectACTIVATING PROTEIN-
dc.subjectGRANULE SECRETION-
dc.subjectCELL RECRUITMENT-
dc.subjectLAMININ ISOFORMS-
dc.subjectNADPH OXIDASE-
dc.titleMST1-dependent vesicle trafficking regulates neutrophil transmigration through the vascular basement membrane-
dc.typeArticle-
dc.identifier.wosid000386992900009-
dc.identifier.scopusid2-s2.0-84994578264-
dc.type.rimsART-
dc.citation.volume126-
dc.citation.issue11-
dc.citation.beginningpage4125-
dc.citation.endingpage4139-
dc.citation.publicationnameJOURNAL OF CLINICAL INVESTIGATION-
dc.identifier.doi10.1172/JCI87043-
dc.contributor.localauthorLim, Dae-Sik-
dc.contributor.nonIdAuthorKurz, Angela R. M.-
dc.contributor.nonIdAuthorPruenster, Monika-
dc.contributor.nonIdAuthorRohwedder, Ina-
dc.contributor.nonIdAuthorRamadass, Mahalakshmi-
dc.contributor.nonIdAuthorSchaefer, Kerstin-
dc.contributor.nonIdAuthorHarrison, Ute-
dc.contributor.nonIdAuthorGouveia, Gabriel-
dc.contributor.nonIdAuthorNussbaum, Claudia-
dc.contributor.nonIdAuthorImmler, Roland-
dc.contributor.nonIdAuthorWiessner, Johannes R.-
dc.contributor.nonIdAuthorMargraf, Andreas-
dc.contributor.nonIdAuthorWalzog, Barbara-
dc.contributor.nonIdAuthorDietzel, Steffen-
dc.contributor.nonIdAuthorMoser, Markus-
dc.contributor.nonIdAuthorKlein, Christoph-
dc.contributor.nonIdAuthorVestweber, Dietmar-
dc.contributor.nonIdAuthorHaas, Rainer-
dc.contributor.nonIdAuthorCatz, Sergio D.-
dc.contributor.nonIdAuthorSperandio, Markus-
dc.type.journalArticleArticle-
dc.subject.keywordPlusIN-VIVO-
dc.subject.keywordPlusLEUKOCYTE MIGRATION-
dc.subject.keywordPlusTRANSENDOTHELIAL MIGRATION-
dc.subject.keywordPlusLYMPHOCYTE TRAFFICKING-
dc.subject.keywordPlusEXTRACELLULAR-MATRIX-
dc.subject.keywordPlusACTIVATING PROTEIN-
dc.subject.keywordPlusGRANULE SECRETION-
dc.subject.keywordPlusCELL RECRUITMENT-
dc.subject.keywordPlusLAMININ ISOFORMS-
dc.subject.keywordPlusNADPH OXIDASE-
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