TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3

Selective autophagy underlies many of the important physiological roles that autophagy plays in multicellular organisms, but the mechanisms involved in cargo selection are poorly understood. Here we describe a molecular mechanism that can target conventional endosomes for autophagic degradation. We...

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Detalles Bibliográficos
Autores: Boada-Romero, Emilio, Letek, Michal, Fleischer, Aarne, Pallauf, Kathrin, Ramón-Barros, Cristina, Pimentel-Muiños, Felipe X.
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2013
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/134321
Acceso en línea:http://hdl.handle.net/10261/134321
Access Level:acceso abierto
Palabra clave:TMEM59
ATG16L1
Autophagy
Vesicle trafficking
WD‐repeat domain
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repository_id_str
spelling TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3Boada-Romero, EmilioLetek, MichalFleischer, AarnePallauf, KathrinRamón-Barros, CristinaPimentel-Muiños, Felipe X.TMEM59ATG16L1AutophagyVesicle traffickingWD‐repeat domainSelective autophagy underlies many of the important physiological roles that autophagy plays in multicellular organisms, but the mechanisms involved in cargo selection are poorly understood. Here we describe a molecular mechanism that can target conventional endosomes for autophagic degradation. We show that the human transmembrane protein TMEM59 contains a minimal 19-amino-acid peptide in its intracellular domain that promotes LC3 labelling and lysosomal targeting of its own endosomal compartment. Interestingly, this peptide defines a novel protein motif that mediates interaction with the WD-repeat domain of ATG16L1, thus providing a mechanistic basis for the activity. The motif is represented with the same ATG16L1-binding ability in other molecules, suggesting a more general relevance. We propose that this motif may play an important role in targeting specific membranous compartments for autophagic degradation, and therefore it may facilitate the search for adaptor proteins that promote selective autophagy by engaging ATG16L1. Endogenous TMEM59 interacts with ATG16L1 and mediates autophagy in response to Staphylococcus aureus infection.This work was funded by grants from the Ministerio de Ciencia e Innovación of the Spanish Government (Refs SAF2008‐00350 and SAF2011‐23714), Fundación Solórzano, Junta de Castilla y León (Consejería de Educación, Ref. CSI001A10‐2, and Consejería de Sanidad) and Consejo Superior de Investigaciones Científicas (CSIC; Ref. 200720I026). Additional funding comes from the FEDER programme of the European Union. EB is a graduate student funded by a predoctoral fellowship from the FPU programme (Ministerio de Educación, MEC, Spanish Government). ML is funded by JAE‐Doc and Juan de la Cierva postdoctoral contracts (MEC and Social European Fund of the European Union, 2007–2013). AF is funded by a long‐term EMBO postdoctoral fellowship and a Juan de la Cierva contract. KP is a graduate student funded by an FPI fellowship (MEC).Peer ReviewedNature Publishing GroupConsejo Superior de Investigaciones Científicas (España)Fundación Memoria de D. Samuel Solorzano BarrusoEuropean CommissionMinisterio de Educación y Cultura (España)Ministerio de Ciencia e Innovación (España)Junta de Castilla y LeónEMBOConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2016201620132016info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Postprintinfo:eu-repo/semantics/acceptedVersionhttp://hdl.handle.net/10261/134321reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttp://dx.doi.org/10.1038/emboj.2013.8Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/1343212026-05-22T06:33:51Z
dc.title.none.fl_str_mv TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3
title TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3
spellingShingle TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3
Boada-Romero, Emilio
TMEM59
ATG16L1
Autophagy
Vesicle trafficking
WD‐repeat domain
title_short TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3
title_full TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3
title_fullStr TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3
title_full_unstemmed TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3
title_sort TMEM59 defines a novel ATG16L1-binding motif that promotes local activation of LC3
dc.creator.none.fl_str_mv Boada-Romero, Emilio
Letek, Michal
Fleischer, Aarne
Pallauf, Kathrin
Ramón-Barros, Cristina
Pimentel-Muiños, Felipe X.
author Boada-Romero, Emilio
author_facet Boada-Romero, Emilio
Letek, Michal
Fleischer, Aarne
Pallauf, Kathrin
Ramón-Barros, Cristina
Pimentel-Muiños, Felipe X.
author_role author
author2 Letek, Michal
Fleischer, Aarne
Pallauf, Kathrin
Ramón-Barros, Cristina
Pimentel-Muiños, Felipe X.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Consejo Superior de Investigaciones Científicas (España)
Fundación Memoria de D. Samuel Solorzano Barruso
European Commission
Ministerio de Educación y Cultura (España)
Ministerio de Ciencia e Innovación (España)
Junta de Castilla y León
EMBO
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv TMEM59
ATG16L1
Autophagy
Vesicle trafficking
WD‐repeat domain
topic TMEM59
ATG16L1
Autophagy
Vesicle trafficking
WD‐repeat domain
description Selective autophagy underlies many of the important physiological roles that autophagy plays in multicellular organisms, but the mechanisms involved in cargo selection are poorly understood. Here we describe a molecular mechanism that can target conventional endosomes for autophagic degradation. We show that the human transmembrane protein TMEM59 contains a minimal 19-amino-acid peptide in its intracellular domain that promotes LC3 labelling and lysosomal targeting of its own endosomal compartment. Interestingly, this peptide defines a novel protein motif that mediates interaction with the WD-repeat domain of ATG16L1, thus providing a mechanistic basis for the activity. The motif is represented with the same ATG16L1-binding ability in other molecules, suggesting a more general relevance. We propose that this motif may play an important role in targeting specific membranous compartments for autophagic degradation, and therefore it may facilitate the search for adaptor proteins that promote selective autophagy by engaging ATG16L1. Endogenous TMEM59 interacts with ATG16L1 and mediates autophagy in response to Staphylococcus aureus infection.
publishDate 2013
dc.date.none.fl_str_mv 2013
2016
2016
2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Postprint
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/134321
url http://hdl.handle.net/10261/134321
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1038/emboj.2013.8
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869422807588274176
score 15.81155

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