Rab27a-mediated protease release regulates neutrophil recruitment by allowing uropod detachment

Detalhes bibliográficos
Autor(a) principal: Singh, Rajesh K.
Data de Publicação: 2012
Outros Autores: Liao, Wenjia, Tracey-White, Dhani, Recchi, Chiara, Tolmachova, Tanya, Rankin, Sara M., Hume, Alistair N., Seabra, Miguel C.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/161893
Resumo: Neutrophil migration is vital for immunity and precedes effector functions such as pathogen killing. Here, we report that this process is regulated by the Rab27a GTPase, a protein known to control granule exocytosis. Rab27a-deficient (Rab27a KO) neutrophils exhibit migration defects in vitro and in vivo, and live-cell microscopy suggests that delayed uropod detachment causes the migratory defect. Surface expression of CD11b, a key adhesion molecule, is increased in chemokine-stimulated Rab27a KO neutrophils compared with the control, suggesting a turnover delay caused by a defect in elastase secretion from azurophilic granules at the rear of bone marrow polymorphonuclear leukocytes (BM-PMNs). We suggest that Rab27a-dependent protease secretion regulates neutrophil migration through proteolysis-dependent de-adhesion of uropods, a mechanism that could be conserved in cell migration and invasion.
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spelling Rab27a-mediated protease release regulates neutrophil recruitment by allowing uropod detachmentCell migrationChemotaxisNeutrophilRab27aUropodCell BiologyNeutrophil migration is vital for immunity and precedes effector functions such as pathogen killing. Here, we report that this process is regulated by the Rab27a GTPase, a protein known to control granule exocytosis. Rab27a-deficient (Rab27a KO) neutrophils exhibit migration defects in vitro and in vivo, and live-cell microscopy suggests that delayed uropod detachment causes the migratory defect. Surface expression of CD11b, a key adhesion molecule, is increased in chemokine-stimulated Rab27a KO neutrophils compared with the control, suggesting a turnover delay caused by a defect in elastase secretion from azurophilic granules at the rear of bone marrow polymorphonuclear leukocytes (BM-PMNs). We suggest that Rab27a-dependent protease secretion regulates neutrophil migration through proteolysis-dependent de-adhesion of uropods, a mechanism that could be conserved in cell migration and invasion.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNSingh, Rajesh K.Liao, WenjiaTracey-White, DhaniRecchi, ChiaraTolmachova, TanyaRankin, Sara M.Hume, Alistair N.Seabra, Miguel C.2024-01-03T23:02:01Z20122012-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article5application/pdfhttp://hdl.handle.net/10362/161893eng0021-9533PURE: 79760757https://doi.org/10.1242/jcs.100438info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:44:43Zoai:run.unl.pt:10362/161893Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:58:41.035646Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Rab27a-mediated protease release regulates neutrophil recruitment by allowing uropod detachment
title Rab27a-mediated protease release regulates neutrophil recruitment by allowing uropod detachment
spellingShingle Rab27a-mediated protease release regulates neutrophil recruitment by allowing uropod detachment
Singh, Rajesh K.
Cell migration
Chemotaxis
Neutrophil
Rab27a
Uropod
Cell Biology
title_short Rab27a-mediated protease release regulates neutrophil recruitment by allowing uropod detachment
title_full Rab27a-mediated protease release regulates neutrophil recruitment by allowing uropod detachment
title_fullStr Rab27a-mediated protease release regulates neutrophil recruitment by allowing uropod detachment
title_full_unstemmed Rab27a-mediated protease release regulates neutrophil recruitment by allowing uropod detachment
title_sort Rab27a-mediated protease release regulates neutrophil recruitment by allowing uropod detachment
author Singh, Rajesh K.
author_facet Singh, Rajesh K.
Liao, Wenjia
Tracey-White, Dhani
Recchi, Chiara
Tolmachova, Tanya
Rankin, Sara M.
Hume, Alistair N.
Seabra, Miguel C.
author_role author
author2 Liao, Wenjia
Tracey-White, Dhani
Recchi, Chiara
Tolmachova, Tanya
Rankin, Sara M.
Hume, Alistair N.
Seabra, Miguel C.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Centro de Estudos de Doenças Crónicas (CEDOC)
RUN
dc.contributor.author.fl_str_mv Singh, Rajesh K.
Liao, Wenjia
Tracey-White, Dhani
Recchi, Chiara
Tolmachova, Tanya
Rankin, Sara M.
Hume, Alistair N.
Seabra, Miguel C.
dc.subject.por.fl_str_mv Cell migration
Chemotaxis
Neutrophil
Rab27a
Uropod
Cell Biology
topic Cell migration
Chemotaxis
Neutrophil
Rab27a
Uropod
Cell Biology
description Neutrophil migration is vital for immunity and precedes effector functions such as pathogen killing. Here, we report that this process is regulated by the Rab27a GTPase, a protein known to control granule exocytosis. Rab27a-deficient (Rab27a KO) neutrophils exhibit migration defects in vitro and in vivo, and live-cell microscopy suggests that delayed uropod detachment causes the migratory defect. Surface expression of CD11b, a key adhesion molecule, is increased in chemokine-stimulated Rab27a KO neutrophils compared with the control, suggesting a turnover delay caused by a defect in elastase secretion from azurophilic granules at the rear of bone marrow polymorphonuclear leukocytes (BM-PMNs). We suggest that Rab27a-dependent protease secretion regulates neutrophil migration through proteolysis-dependent de-adhesion of uropods, a mechanism that could be conserved in cell migration and invasion.
publishDate 2012
dc.date.none.fl_str_mv 2012
2012-01-01T00:00:00Z
2024-01-03T23:02:01Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/161893
url http://hdl.handle.net/10362/161893
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0021-9533
PURE: 79760757
https://doi.org/10.1242/jcs.100438
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 5
application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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