The T300A Crohn’s disease risk polymorphism impairs function of the WD40 domain of ATG16L1

Article number: 11821 (2016)

Detalles Bibliográficos
Autores: Boada-Romero, Emilio, Serramito Gómez, Inmaculada, Sacristán Martín, María Paz, Boone, David L., Xavier, Ramnik J., Pimentel Muiños, Felipe Xosé
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/155918
Acceso en línea:http://hdl.handle.net/10366/155918
Access Level:acceso abierto
Palabra clave:Autophagy
Crohn Disease
2415 Biología Molecular
2407 Biología Celular
2302 Bioquímica
enfermedad de Crohn
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spelling The T300A Crohn’s disease risk polymorphism impairs function of the WD40 domain of ATG16L1Boada-Romero, EmilioSerramito Gómez, InmaculadaSacristán Martín, María PazBoone, David L.Xavier, Ramnik J.Pimentel Muiños, Felipe XoséAutophagyCrohn Disease2415 Biología Molecular2407 Biología Celular2302 Bioquímicaenfermedad de CrohnArticle number: 11821 (2016)[EN]A coding polymorphism of human ATG16L1 (rs2241880; T300A) increases the risk of Crohn’s disease and it has been shown to enhance susceptibility of ATG16L1 to caspase cleavage. Here we show that T300A also alters the ability of the C-terminal WD40-repeat domain of ATG16L1 to interact with an amino acid motif that recognizes this region. Such alteration impairs the unconventional autophagic activity of TMEM59, a transmembrane protein that contains the WD40 domain-binding motif, and disrupts its normal intracellular trafficking and its ability to engage ATG16L1 in response to bacterial infection. TMEM59-induced autophagy is blunted in cells expressing the fragments generated by caspase processing of the ATG16L1-T300A risk allele, whereas canonical autophagy remains unaffected. These results suggest that the T300A polymorphism alters the function of motif-containing molecules that engage ATG16L1 through the WD40 domain, either by influencing this interaction under non-stressful conditions or by inhibiting their downstream autophagic signalling after caspase-mediated cleavage.Nature Research202420242016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10366/155918reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)InglésSAF2011-23714SAF2014-53320-RCSI001A10-2, FIC016U14CC0 1.0 Universalhttp://creativecommons.org/publicdomain/zero/1.0/info:eu-repo/semantics/openAccessoai:gredos.usal.es:10366/1559182026-06-07T06:28:51Z
dc.title.none.fl_str_mv The T300A Crohn’s disease risk polymorphism impairs function of the WD40 domain of ATG16L1
title The T300A Crohn’s disease risk polymorphism impairs function of the WD40 domain of ATG16L1
spellingShingle The T300A Crohn’s disease risk polymorphism impairs function of the WD40 domain of ATG16L1
Boada-Romero, Emilio
Autophagy
Crohn Disease
2415 Biología Molecular
2407 Biología Celular
2302 Bioquímica
enfermedad de Crohn
title_short The T300A Crohn’s disease risk polymorphism impairs function of the WD40 domain of ATG16L1
title_full The T300A Crohn’s disease risk polymorphism impairs function of the WD40 domain of ATG16L1
title_fullStr The T300A Crohn’s disease risk polymorphism impairs function of the WD40 domain of ATG16L1
title_full_unstemmed The T300A Crohn’s disease risk polymorphism impairs function of the WD40 domain of ATG16L1
title_sort The T300A Crohn’s disease risk polymorphism impairs function of the WD40 domain of ATG16L1
dc.creator.none.fl_str_mv Boada-Romero, Emilio
Serramito Gómez, Inmaculada
Sacristán Martín, María Paz
Boone, David L.
Xavier, Ramnik J.
Pimentel Muiños, Felipe Xosé
author Boada-Romero, Emilio
author_facet Boada-Romero, Emilio
Serramito Gómez, Inmaculada
Sacristán Martín, María Paz
Boone, David L.
Xavier, Ramnik J.
Pimentel Muiños, Felipe Xosé
author_role author
author2 Serramito Gómez, Inmaculada
Sacristán Martín, María Paz
Boone, David L.
Xavier, Ramnik J.
Pimentel Muiños, Felipe Xosé
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Autophagy
Crohn Disease
2415 Biología Molecular
2407 Biología Celular
2302 Bioquímica
enfermedad de Crohn
topic Autophagy
Crohn Disease
2415 Biología Molecular
2407 Biología Celular
2302 Bioquímica
enfermedad de Crohn
description Article number: 11821 (2016)
publishDate 2016
dc.date.none.fl_str_mv 2016
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10366/155918
url http://hdl.handle.net/10366/155918
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv SAF2011-23714
SAF2014-53320-R
CSI001A10-2, FIC016U14
dc.rights.none.fl_str_mv CC0 1.0 Universal
http://creativecommons.org/publicdomain/zero/1.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv CC0 1.0 Universal
http://creativecommons.org/publicdomain/zero/1.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Nature Research
publisher.none.fl_str_mv Nature Research
dc.source.none.fl_str_mv reponame:GREDOS. Repositorio Institucional de la Universidad de Salamanca
instname:Universidad de Salamanca (USAL)
instname_str Universidad de Salamanca (USAL)
reponame_str GREDOS. Repositorio Institucional de la Universidad de Salamanca
collection GREDOS. Repositorio Institucional de la Universidad de Salamanca
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300724

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