Effect of ATG12–ATG5-ATG16L1 autophagy E3-like complex on the ability of LC3/GABARAP proteins to induce vesicle tethering and fusion
dc.contributor.author | Iriondo Nagore, Marina | |
dc.contributor.author | Etxaniz Iriondo, Asier | |
dc.contributor.author | Varela Fernández, Yaiza | |
dc.contributor.author | Ballesteros Rivero, Uxue | |
dc.contributor.author | Lázaro, Melisa | |
dc.contributor.author | Valle, Mikel | |
dc.contributor.author | Fracchiolla, Dorotea | |
dc.contributor.author | Martens, Sascha | |
dc.contributor.author | Montes Burgos, Lidia Ruth ![]() | |
dc.contributor.author | Goñi Urcelay, Félix María ![]() | |
dc.contributor.author | Alonso Izquierdo, Alicia ![]() | |
dc.date.accessioned | 2023-02-15T18:00:22Z | |
dc.date.available | 2023-02-15T18:00:22Z | |
dc.date.issued | 2023-02 | |
dc.identifier.citation | Cellular and Molecular Life Sciences 80(2) : (2023) // Article ID 56 | es_ES |
dc.identifier.issn | 1420-9071 | |
dc.identifier.uri | http://hdl.handle.net/10810/59871 | |
dc.description.abstract | In macroautophagy, the autophagosome (AP) engulfs portions of cytoplasm to allow their lysosomal degradation. AP formation in humans requires the concerted action of the ATG12 and LC3/GABARAP conjugation systems. The ATG12–ATG5-ATG16L1 or E3-like complex (E3 for short) acts as a ubiquitin-like E3 enzyme, promoting LC3/GABARAP proteins anchoring to the AP membrane. Their role in the AP expansion process is still unclear, in part because there are no studies comparing six LC3/GABARAP family member roles under the same conditions, and also because the full human E3 was only recently available. In the present study, the lipidation of six members of the LC3/GABARAP family has been reconstituted in the presence and absence of E3, and the mechanisms by which E3 and LC3/GABARAP proteins participate in vesicle tethering and fusion have been investigated. In the absence of E3, GABARAP and GABARAPL1 showed the highest activities. Differences found within LC3/GABARAP proteins suggest the existence of a lipidation threshold, lower for the GABARAP subfamily, as a requisite for tethering and inter-vesicular lipid mixing. E3 increases and speeds up lipidation and LC3/GABARAP-promoted tethering. However, E3 hampers LC3/GABARAP capacity to induce inter-vesicular lipid mixing or subsequent fusion, presumably through the formation of a rigid scaffold on the vesicle surface. Our results suggest a model of AP expansion in which the growing regions would be areas where the LC3/GABARAP proteins involved should be susceptible to lipidation in the absence of E3, or else a regulatory mechanism would allow vesicle incorporation and phagophore growth when E3 is present. | es_ES |
dc.description.sponsorship | This work was supported in part by the Spanish Ministerio de Ciencia e Innovación (MCI), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER) (grants No. PGC2018-099857-B-I00 and PID2021-124461NB-I00), by the Basque Government (grants No. IT1625-22 and IT1270-19), by Fundación Biofísica Bizkaia, by Fundación Ramón Areces (grant No. CIVP20A6619), and by the Basque Excellence Research Centre (BERC) program of the Basque Government. MI and YV were recipients of predoctoral FPU fellowships from the Spanish Ministry of Science, Innovation and Universities (FPU16/05873, FPU18/00799), UB thanks the University of the Basque Country for a predoctoral contract. This work was supported by Human Frontiers Science Program RGP0026/2017 (S.M.). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Springer | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/PGC2018-099857-B-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2021-124461NB-I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.title | Effect of ATG12–ATG5-ATG16L1 autophagy E3-like complex on the ability of LC3/GABARAP proteins to induce vesicle tethering and fusion | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © The Author(s) 2023. This article is licensed under a Creative Commons Attri- bution 4.0 International License, which permits use, sharing, adapta- tion, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://link.springer.com/article/10.1007/s00018-023-04704-z | es_ES |
dc.identifier.doi | 10.1007/s00018-023-04704-z | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |
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