A conserved ATG2 binding site in WIPI4 and yeast Hsv2 is disrupted by mutations causing ß-propeller protein-associated neurodegeneration

© The Author(s) 2021.

Detalles Bibliográficos
Autores: Bueno Arribas, M., Blanca, Irene, Cruz-Cuevas, Celia, Escalante, Ricardo, Navas, María-Angeles, Vincent, Olivier
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/264776
Acceso en línea:http://hdl.handle.net/10261/264776
Access Level:acceso abierto
Palabra clave:Mutation
Autophagy
Binding sites
Endosomes
Human herpesvirus 2
Nerve degeneration
Yeasts
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spelling A conserved ATG2 binding site in WIPI4 and yeast Hsv2 is disrupted by mutations causing ß-propeller protein-associated neurodegenerationBueno Arribas, M.Blanca, IreneCruz-Cuevas, CeliaEscalante, RicardoNavas, María-AngelesVincent, OlivierMutationAutophagyBinding sitesEndosomesHuman herpesvirus 2Nerve degenerationYeasts© The Author(s) 2021.PROPPINs are phosphoinositide-binding β-propeller proteins that mediate membrane recruitment of other proteins and are involved in different membrane remodeling processes. The main role of PROPPINs is their function in autophagy, where they act at different steps in phagophore formation. The human PROPPIN WIPI4 (WDR45) forms a complex with ATG2 involved in phagophore elongation, and mutations in this gene cause β-propeller protein-associated neurodegeneration (BPAN). The yeast functional counterpart of WIPI4 is Atg18, although its closest sequence homolog is another member of the PROPPIN family, Hsv2, whose function remains largely undefined. Here, we provide evidence that Hsv2, like WIPI4 and Atg18, interacts with Atg2. We show that Hsv2 and a pool of Atg2 colocalize on endosomes under basal conditions and at the pre-autophagosomal structure (PAS) upon autophagy induction. We further show that Hsv2 drives the recruitment of Atg2 to endosomes while Atg2 mediates Hsv2 recruitment to the PAS. HSV2 overexpression results in mis-sorting and secretion of carboxypeptidase CPY, suggesting that the endosomal function of this protein is related to the endosome-to-Golgi recycling pathway. Furthermore, we show that the Atg2 binding site is conserved in Hsv2 and WIPI4 but not in Atg18. Notably, two WIPI4 residues involved in ATG2 binding are mutated in patients with BPAN, and there is a correlation between the inhibitory effect of these mutations on ATG2 binding and the severity of the disease.Ministerio de Ciencia, Innovación y Universidades, grant number [PGC2018-093604-B-I00] (MCIU/AEI/FEDER,UE); Formación de Profesorado Universitario (FPU) program from the Ministerio de Ciencia, Innovación y Universidades (to M.B.-A.); Garantía Juvenil Program from Comunidad de Madrid (to C.C-.C.).Oxford University PressMinisterio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Comunidad de MadridConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2022202220222022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/264776reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-093604-B-I00http://dx.doi.org/10.1093/hmg/ddab225Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2647762026-05-22T06:33:51Z
dc.title.none.fl_str_mv A conserved ATG2 binding site in WIPI4 and yeast Hsv2 is disrupted by mutations causing ß-propeller protein-associated neurodegeneration
title A conserved ATG2 binding site in WIPI4 and yeast Hsv2 is disrupted by mutations causing ß-propeller protein-associated neurodegeneration
spellingShingle A conserved ATG2 binding site in WIPI4 and yeast Hsv2 is disrupted by mutations causing ß-propeller protein-associated neurodegeneration
Bueno Arribas, M.
Mutation
Autophagy
Binding sites
Endosomes
Human herpesvirus 2
Nerve degeneration
Yeasts
title_short A conserved ATG2 binding site in WIPI4 and yeast Hsv2 is disrupted by mutations causing ß-propeller protein-associated neurodegeneration
title_full A conserved ATG2 binding site in WIPI4 and yeast Hsv2 is disrupted by mutations causing ß-propeller protein-associated neurodegeneration
title_fullStr A conserved ATG2 binding site in WIPI4 and yeast Hsv2 is disrupted by mutations causing ß-propeller protein-associated neurodegeneration
title_full_unstemmed A conserved ATG2 binding site in WIPI4 and yeast Hsv2 is disrupted by mutations causing ß-propeller protein-associated neurodegeneration
title_sort A conserved ATG2 binding site in WIPI4 and yeast Hsv2 is disrupted by mutations causing ß-propeller protein-associated neurodegeneration
dc.creator.none.fl_str_mv Bueno Arribas, M.
Blanca, Irene
Cruz-Cuevas, Celia
Escalante, Ricardo
Navas, María-Angeles
Vincent, Olivier
author Bueno Arribas, M.
author_facet Bueno Arribas, M.
Blanca, Irene
Cruz-Cuevas, Celia
Escalante, Ricardo
Navas, María-Angeles
Vincent, Olivier
author_role author
author2 Blanca, Irene
Cruz-Cuevas, Celia
Escalante, Ricardo
Navas, María-Angeles
Vincent, Olivier
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Comunidad de Madrid
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Mutation
Autophagy
Binding sites
Endosomes
Human herpesvirus 2
Nerve degeneration
Yeasts
topic Mutation
Autophagy
Binding sites
Endosomes
Human herpesvirus 2
Nerve degeneration
Yeasts
description © The Author(s) 2021.
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
2022
2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/264776
url http://hdl.handle.net/10261/264776
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-093604-B-I00
http://dx.doi.org/10.1093/hmg/ddab225
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Oxford University Press
publisher.none.fl_str_mv Oxford University Press
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
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score 15,811543

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