Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes

Detalhes bibliográficos
Autor(a) principal: Westerberg, Lisa S.
Data de Publicação: 2010
Outros Autores: Meelu, Parool, Baptista, Marisa, Eston, Michelle A., Adamovich, David A., Almeida, Vinicius Cotta de, Seed, Brian, Rosen, Michael K., Vandenberghe, Peter, Thrasher, Adrian J., Klein, Christoph, Alt, Frederick W., Snapper, Scott B.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/26608
Resumo: Massachusetts General Hospital. Gastrointestinal Unit. Center for the Study of Inflammatory Bowel Diseases. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA / Karolinska Institute. Department of Medicine. Unit of Clinical Allergy research. Stockholm, Sweden.
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spelling Westerberg, Lisa S.Meelu, ParoolBaptista, MarisaEston, Michelle A.Adamovich, David A.Almeida, Vinicius Cotta deSeed, BrianRosen, Michael K.Vandenberghe, PeterThrasher, Adrian J.Klein, ChristophAlt, Frederick W.Snapper, Scott B.2018-05-24T12:34:36Z2018-05-24T12:34:36Z2010WESTERBERG, Lisa S. et al. Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes. J. Exp. Med., v.207, n. 6, p.1145-1152, 2009.0022-1007https://www.arca.fiocruz.br/handle/icict/2660810.1084/jem.200912451540-9538engRockefeller University PressMutações ativadoras de WASPcélulas linfocitáriasestabilidade genômicacélulas B e TX-linked neutropeniaWASP-activating mutationsB and T cellslymphocyte cell survivalgenomic stabilityneutropeniaActivating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleMassachusetts General Hospital. Gastrointestinal Unit. Center for the Study of Inflammatory Bowel Diseases. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA / Karolinska Institute. Department of Medicine. Unit of Clinical Allergy research. Stockholm, Sweden.Massachusetts General Hospital. Gastrointestinal Unit. Center for the Study of Inflammatory Bowel Diseases. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA.Karolinska Institute. Department of Medicine. Unit of Clinical Allergy research. Stockholm, Sweden.Massachusetts General Hospital. Gastrointestinal Unit. Center for the Study of Inflammatory Bowel Diseases. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA.Massachusetts General Hospital. Gastrointestinal Unit. Center for the Study of Inflammatory Bowel Diseases. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA.Massachusetts General Hospital. Gastrointestinal Unit. Center for the Study of Inflammatory Bowel Diseases. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Massachusetts General Hospital. Center for Computational and Integrative Biology. Boston, MA, USA / Harvard Medical School. Department of Genetics. Boston, MA, USA.University of Texas Southwestern Medical Center. University of Texas Southwestern Medical Center. Dallas, TX, USA.University Hospital Leuven and University of Leuven. Center for Human Genetics. Leuven, Belgium / University Hospital Leuven and University of Leuven.. Department of Hematology. Leuven, Belgium.University College London. UCL Institute of Child Health. Molecular Immunology Unit. London, England, UK.Hannover Medical School. Department of Pediatric Hematology and Oncology. Hannover, Germany.Harvard Medical School. Departments of Genetics. Boston, MA, USA /Harvard Medical School. Howard Hughes Medical Institute.Boston, MA, USA.Massachusetts General Hospital. Gastrointestinal Unit. Center for the Study of Inflammatory Bowel Diseases. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA.X-linked neutropenia (XLN) is caused by activating mutations in the Wiskott-Aldrich syndrome protein (WASP) that result in aberrant autoinhibition. Although patients with XLN appear to have only defects in myeloid lineages, we hypothesized that activating mutations of WASP are likely to affect the immune system more broadly. We generated mouse models to assess the role of activating WASP mutations associated with XLN (XLN-WASP) in lymphocytes. XLN-WASP is expressed stably in B and T cells and induces a marked increase in polymerized actin. XLN-WASP-expressing B and T cells migrate toward chemokines but fail to adhere normally. In marked contrast to WASP-deficient cells, XLN-WASP-expressing T cells proliferate normally in response to cell-surface receptor activation. However, XLN-WASP-expressing B cells fail to proliferate and secrete lower amounts of antibodies. Moreover, XLN-WASP expression in lymphocytes results in modestly increased apoptosis associated with increased genomic instability. These data indicate that there are unique requirements for the presence and activation status of WASP in B and T cells and that WASP-activating mutations interfere with lymphocyte cell survival and genomic stability.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/26608/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALviniciuscotta_almeida_etal_IOC_2010.pdfviniciuscotta_almeida_etal_IOC_2010.pdfapplication/pdf2974240https://www.arca.fiocruz.br/bitstream/icict/26608/2/viniciuscotta_almeida_etal_IOC_2010.pdf4f93ecc09aa938fa3cd3e6e144303fb6MD52TEXTviniciuscotta_almeida_etal_IOC_2010.pdf.txtviniciuscotta_almeida_etal_IOC_2010.pdf.txtExtracted 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dc.title.pt_BR.fl_str_mv Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes
title Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes
spellingShingle Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes
Westerberg, Lisa S.
Mutações ativadoras de WASP
células linfocitárias
estabilidade genômica
células B e T
X-linked neutropenia
WASP-activating mutations
B and T cells
lymphocyte cell survival
genomic stability
neutropenia
title_short Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes
title_full Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes
title_fullStr Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes
title_full_unstemmed Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes
title_sort Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes
author Westerberg, Lisa S.
author_facet Westerberg, Lisa S.
Meelu, Parool
Baptista, Marisa
Eston, Michelle A.
Adamovich, David A.
Almeida, Vinicius Cotta de
Seed, Brian
Rosen, Michael K.
Vandenberghe, Peter
Thrasher, Adrian J.
Klein, Christoph
Alt, Frederick W.
Snapper, Scott B.
author_role author
author2 Meelu, Parool
Baptista, Marisa
Eston, Michelle A.
Adamovich, David A.
Almeida, Vinicius Cotta de
Seed, Brian
Rosen, Michael K.
Vandenberghe, Peter
Thrasher, Adrian J.
Klein, Christoph
Alt, Frederick W.
Snapper, Scott B.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Westerberg, Lisa S.
Meelu, Parool
Baptista, Marisa
Eston, Michelle A.
Adamovich, David A.
Almeida, Vinicius Cotta de
Seed, Brian
Rosen, Michael K.
Vandenberghe, Peter
Thrasher, Adrian J.
Klein, Christoph
Alt, Frederick W.
Snapper, Scott B.
dc.subject.other.pt_BR.fl_str_mv Mutações ativadoras de WASP
células linfocitárias
estabilidade genômica
células B e T
X-linked neutropenia
topic Mutações ativadoras de WASP
células linfocitárias
estabilidade genômica
células B e T
X-linked neutropenia
WASP-activating mutations
B and T cells
lymphocyte cell survival
genomic stability
neutropenia
dc.subject.en.pt_BR.fl_str_mv WASP-activating mutations
B and T cells
lymphocyte cell survival
genomic stability
neutropenia
description Massachusetts General Hospital. Gastrointestinal Unit. Center for the Study of Inflammatory Bowel Diseases. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA / Karolinska Institute. Department of Medicine. Unit of Clinical Allergy research. Stockholm, Sweden.
publishDate 2010
dc.date.issued.fl_str_mv 2010
dc.date.accessioned.fl_str_mv 2018-05-24T12:34:36Z
dc.date.available.fl_str_mv 2018-05-24T12:34:36Z
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.citation.fl_str_mv WESTERBERG, Lisa S. et al. Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes. J. Exp. Med., v.207, n. 6, p.1145-1152, 2009.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/26608
dc.identifier.issn.pt_BR.fl_str_mv 0022-1007
dc.identifier.doi.none.fl_str_mv 10.1084/jem.20091245
dc.identifier.eissn.none.fl_str_mv 1540-9538
identifier_str_mv WESTERBERG, Lisa S. et al. Activating WASP mutations associated with X-linked neutropenia result in enhanced actin polymerization, altered cytoskeletal responses, and genomic instability in lymphocytes. J. Exp. Med., v.207, n. 6, p.1145-1152, 2009.
0022-1007
10.1084/jem.20091245
1540-9538
url https://www.arca.fiocruz.br/handle/icict/26608
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Rockefeller University Press
publisher.none.fl_str_mv Rockefeller University Press
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
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