Role of cortactin and the adaptor proteins NCK and CRK in pedestal formation by entherpathogenic "Escherichia coli" enteropatógena (EPEC).

The adherence of enteropathogenic Escherichia coli (EPEC) to human intestinal cells triggers the formation of actin-rich pedestals. This process requires the translocation of the bacterial translocated intimin receptor (Tir) into host cells through a type III secretion system. The insertion of Tir i...

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Detalhes bibliográficos
Autor: Nieto Pelegrín, Elvira
Formato: tesis doctoral
Fecha de publicación:2013
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/37434
Acesso em linha:https://hdl.handle.net/20.500.14352/37434
Access Level:acceso abierto
Palavra-chave:579.842.1/.2(043.2)
Escherichia coli enteropatógena (EPEC)/cortactina/Crk/Nck Enteropathogenic Escherichia coli (EPEC)/cortactin/Crk/Nck
Microbiología (Farmacia)
3302.03 Microbiología Industrial
id ES_f575150ba992eebbd1ebd10e30a324ff
oai_identifier_str oai:docta.ucm.es:20.500.14352/37434
network_acronym_str ES
network_name_str España
repository_id_str
spelling Role of cortactin and the adaptor proteins NCK and CRK in pedestal formation by entherpathogenic "Escherichia coli" enteropatógena (EPEC).Papel de cortactina y de las proteínas adaptadoras Nck y Crk en la formación del pedestal por "Escherichia coli" enteropatógena (EPEC)Nieto Pelegrín, Elvira579.842.1/.2(043.2)Escherichia coli enteropatógena (EPEC)/cortactina/Crk/Nck Enteropathogenic Escherichia coli (EPEC)/cortactin/Crk/NckMicrobiología (Farmacia)3302.03 Microbiología IndustrialThe adherence of enteropathogenic Escherichia coli (EPEC) to human intestinal cells triggers the formation of actin-rich pedestals. This process requires the translocation of the bacterial translocated intimin receptor (Tir) into host cells through a type III secretion system. The insertion of Tir into the plasma membrane and its tyrosine-phosphorylation leads to the recruitment of the host cell adaptor Nck, following Tir interaction with its ligand -the EPEC intimin surface protein. Nck in turn activates the neural Wiskott-Aldrich syndrome protein (N-WASP) initiating actin polymerisation mediated by the actin-related (Arp)2/3 complex. Interestingly, the host cortactin protein activates the Arp2/3 complex and N-WASP promoting actin polymerisation by two different mechanisms. Here, we interrogate a suggested role for cortactin in Tir-mediated actin nucleation events and reveal a critical role. We propose that cortactin binds Tir through its N-terminal part in a phosphorylation independent manner. On the other hand, the SH3 domain binding and activation of N-WASP is regulated by tyrosine and serine mediated phosphorylation of cortactin. Moreover, Tir-cortactin interaction promotes Arp2/3 complex-mediated actin polymerisation in vitro. Therefore, cortactin could act on Tir:Nck:N-WASP signalling pathway and control a possible cycling activity of N-WASP underlying pedestal formation. We also demonstrate that Crk family adaptor proteins have a redundant inhibitory role in regulating actin polymerisation in actin pedestals. Furthermore, we have investigated the mechanism of the observed reduced amounts of Tir in infected Nck deficient mouse embryonic fibroblast (MEFs).Universidad Complutense de MadridMartínez Quíles, NarcisaUniversidad Complutense de Madrid20132013-04-2320132013-04-23doctoral thesishttp://purl.org/coar/resource_type/c_db06info:eu-repo/semantics/doctoralThesisapplication/pdfhttps://hdl.handle.net/20.500.14352/37434reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/374342026-06-02T12:44:21Z
dc.title.none.fl_str_mv Role of cortactin and the adaptor proteins NCK and CRK in pedestal formation by entherpathogenic "Escherichia coli" enteropatógena (EPEC).
Papel de cortactina y de las proteínas adaptadoras Nck y Crk en la formación del pedestal por "Escherichia coli" enteropatógena (EPEC)
title Role of cortactin and the adaptor proteins NCK and CRK in pedestal formation by entherpathogenic "Escherichia coli" enteropatógena (EPEC).
spellingShingle Role of cortactin and the adaptor proteins NCK and CRK in pedestal formation by entherpathogenic "Escherichia coli" enteropatógena (EPEC).
Nieto Pelegrín, Elvira
579.842.1/.2(043.2)
Escherichia coli enteropatógena (EPEC)/cortactina/Crk/Nck Enteropathogenic Escherichia coli (EPEC)/cortactin/Crk/Nck
Microbiología (Farmacia)
3302.03 Microbiología Industrial
title_short Role of cortactin and the adaptor proteins NCK and CRK in pedestal formation by entherpathogenic "Escherichia coli" enteropatógena (EPEC).
title_full Role of cortactin and the adaptor proteins NCK and CRK in pedestal formation by entherpathogenic "Escherichia coli" enteropatógena (EPEC).
title_fullStr Role of cortactin and the adaptor proteins NCK and CRK in pedestal formation by entherpathogenic "Escherichia coli" enteropatógena (EPEC).
title_full_unstemmed Role of cortactin and the adaptor proteins NCK and CRK in pedestal formation by entherpathogenic "Escherichia coli" enteropatógena (EPEC).
title_sort Role of cortactin and the adaptor proteins NCK and CRK in pedestal formation by entherpathogenic "Escherichia coli" enteropatógena (EPEC).
dc.creator.none.fl_str_mv Nieto Pelegrín, Elvira
author Nieto Pelegrín, Elvira
author_facet Nieto Pelegrín, Elvira
author_role author
dc.contributor.none.fl_str_mv Martínez Quíles, Narcisa
Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 579.842.1/.2(043.2)
Escherichia coli enteropatógena (EPEC)/cortactina/Crk/Nck Enteropathogenic Escherichia coli (EPEC)/cortactin/Crk/Nck
Microbiología (Farmacia)
3302.03 Microbiología Industrial
topic 579.842.1/.2(043.2)
Escherichia coli enteropatógena (EPEC)/cortactina/Crk/Nck Enteropathogenic Escherichia coli (EPEC)/cortactin/Crk/Nck
Microbiología (Farmacia)
3302.03 Microbiología Industrial
description The adherence of enteropathogenic Escherichia coli (EPEC) to human intestinal cells triggers the formation of actin-rich pedestals. This process requires the translocation of the bacterial translocated intimin receptor (Tir) into host cells through a type III secretion system. The insertion of Tir into the plasma membrane and its tyrosine-phosphorylation leads to the recruitment of the host cell adaptor Nck, following Tir interaction with its ligand -the EPEC intimin surface protein. Nck in turn activates the neural Wiskott-Aldrich syndrome protein (N-WASP) initiating actin polymerisation mediated by the actin-related (Arp)2/3 complex. Interestingly, the host cortactin protein activates the Arp2/3 complex and N-WASP promoting actin polymerisation by two different mechanisms. Here, we interrogate a suggested role for cortactin in Tir-mediated actin nucleation events and reveal a critical role. We propose that cortactin binds Tir through its N-terminal part in a phosphorylation independent manner. On the other hand, the SH3 domain binding and activation of N-WASP is regulated by tyrosine and serine mediated phosphorylation of cortactin. Moreover, Tir-cortactin interaction promotes Arp2/3 complex-mediated actin polymerisation in vitro. Therefore, cortactin could act on Tir:Nck:N-WASP signalling pathway and control a possible cycling activity of N-WASP underlying pedestal formation. We also demonstrate that Crk family adaptor proteins have a redundant inhibitory role in regulating actin polymerisation in actin pedestals. Furthermore, we have investigated the mechanism of the observed reduced amounts of Tir in infected Nck deficient mouse embryonic fibroblast (MEFs).
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-04-23
2013
2013-04-23
dc.type.none.fl_str_mv doctoral thesis
http://purl.org/coar/resource_type/c_db06
dc.type.openaire.fl_str_mv info:eu-repo/semantics/doctoralThesis
format doctoralThesis
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/37434
url https://hdl.handle.net/20.500.14352/37434
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidad Complutense de Madrid
publisher.none.fl_str_mv Universidad Complutense de Madrid
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869424591744532480
score 15.300724

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