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/10362/21954
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 detachmentNeutrophilEFFECTORSGRANULESELASTASEGRISCELLI-SYNDROMECell migrationChemotaxisRAB27AINFLAMMATIONIMMUNITYEXOCYTOSISCELLSACTIVATIONUropodRab27aChemotaxisCell migrationNeutrophilUropodNeutrophil 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.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNSingh, Rajesh KLiao, WenjiaTracey-White,  DhaniRecchi, ChiaraTolmachova, TanyaRankin, Sara MHume, Alistair NSeabra, Miguel C2017-07-14T22:00:42Z2012-04-012012-04-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article5application/pdfhttp://hdl.handle.net/10362/21954eng0021-9533PURE: 234515https://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:RCAAP2023-11-21T11:41:30Zoai:run.unl.pt:10362/21954Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T23:18:49.589680Repositório 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
Neutrophil
EFFECTORS
GRANULES
ELASTASE
GRISCELLI-SYNDROME
Cell migration
Chemotaxis
RAB27A
INFLAMMATION
IMMUNITY
EXOCYTOSIS
CELLS
ACTIVATION
Uropod
Rab27a
Chemotaxis
Cell migration
Neutrophil
Uropod
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 Centro de Estudos de Doenças Crónicas (CEDOC)
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
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 Neutrophil
EFFECTORS
GRANULES
ELASTASE
GRISCELLI-SYNDROME
Cell migration
Chemotaxis
RAB27A
INFLAMMATION
IMMUNITY
EXOCYTOSIS
CELLS
ACTIVATION
Uropod
Rab27a
Chemotaxis
Cell migration
Neutrophil
Uropod
topic Neutrophil
EFFECTORS
GRANULES
ELASTASE
GRISCELLI-SYNDROME
Cell migration
Chemotaxis
RAB27A
INFLAMMATION
IMMUNITY
EXOCYTOSIS
CELLS
ACTIVATION
Uropod
Rab27a
Chemotaxis
Cell migration
Neutrophil
Uropod
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 2012-04-01
2012-04-01T00:00:00Z
2017-07-14T22:00:42Z
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/10362/21954
url http://hdl.handle.net/10362/21954
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0021-9533
PURE: 234515
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
institution RCAAP
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
repository.mail.fl_str_mv
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