dc.contributor.author | Cabezudo, Sofía | |
dc.contributor.author | Sanz-Flores, Maria | |
dc.contributor.author | Caballero, Alvaro | |
dc.contributor.author | Tasset, Inmaculada | |
dc.contributor.author | Rebollo, Elena | |
dc.contributor.author | Diaz, Antonio | |
dc.contributor.author | Aragay, Anna M | |
dc.contributor.author | Cuervo, Ana María | |
dc.contributor.author | Mayor, Federico | |
dc.contributor.author | Ribas, Catalina | |
dc.date.accessioned | 2021-08-27T10:45:53Z | |
dc.date.available | 2021-08-27T10:45:53Z | |
dc.date.issued | 2021-07-27 | |
dc.identifier.citation | Nat Commun.2021;12(1):4540. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/13322 | |
dc.description.abstract | The mTORC1 node plays a major role in autophagy modulation. We report a role of the ubiquitous Gαq subunit, a known transducer of plasma membrane G protein-coupled receptors signaling, as a core modulator of mTORC1 and autophagy. Cells lacking Gαq/11 display higher basal autophagy, enhanced autophagy induction upon different types of nutrient stress along with a decreased mTORC1 activation status. They are also unable to reactivate mTORC1 and thus inactivate ongoing autophagy upon nutrient recovery. Conversely, stimulation of Gαq/11 promotes sustained mTORC1 pathway activation and reversion of autophagy promoted by serum or amino acids removal. Gαq is present in autophagic compartments and lysosomes and is part of the mTORC1 multi-molecular complex, contributing to its assembly and activation via its nutrient status-sensitive interaction with p62, which displays features of a Gαq effector. Gαq emerges as a central regulator of the autophagy machinery required to maintain cellular homeostasis upon nutrient fluctuations. | es_ES |
dc.description.sponsorship | We thank Paula Ramos, Susana Rojo-Berciano, and Laura López for helpful technicalassistance. Dr. Marta Cruces (Universidad Autónoma de Madrid, Spain) for herinvaluable help regarding the liver explants experiments, Dr. Badford Berk (University ofRochester, NY, USA) for providing the GFP-Flag-PB1-p62 plasmid, Drs. Stefan Offer-manns and Nina Wettschureck (Max-Planck-Institute for Heart and Lung Research,Germany) for providing Tie2-CreERT2; Gnaq f/f; Gna11−/−[EC-q/11-KO) mice, andDr. Guzmán Sánchez for scientific advice. We thank also Ricardo Ramos from theGenomic facility of Fundación Parque Científico de Madrid (Universidad Autónoma deMadrid, Spain) and Gemma Rodríguez-Tarduchy from the Genomic facility of theInstituto de Investigaciones Biomédicas“Alberto Sols”for their help with cell linesauthentication. The help from CBMSO Animal Care, Flow Cytometry, Electron andOptical and Confocal Microscopy facilities is also acknowledged. This work was sup-ported by Ministerio de Economía; Industria y Competitividad (MINECO) of Spain(grant SAF2017-84125-R to F.M.), (grant BFU2017-83379-R to A.M.A.), Instituto deSalud Carlos III (PI18/01662 to CR, co-funded with European FEDER contribution),CIBERCV-Instituto de Salud Carlos III, Spain (grant CB16/11/00278 to F.M., co-fundedwith European FEDER contribution), Fundación Ramón Areces (to C.R. and F.M.) andPrograma de Actividades en Biomedicina de la Comunidad de Madrid-B2017/BMD-3671-INFLAMUNE to F.M. and NIH grants AG021904 and AG038072 to A.M.C. Wealso acknowledge the support of a Contrato para la Formación del Profesorado Uni-versitario (FPU13/04341) and (FPU14/06670), an EMBO short-term fellowship (ASTF600-2016). We also acknowledge institutional support to the CBMSO from FundaciónRamón Areces. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-sa/4.0/ | * |
dc.subject.mesh | Autophagy | es_ES |
dc.subject.mesh | Signal Transduction | es_ES |
dc.subject.mesh | Animals | es_ES |
dc.subject.mesh | CHO Cells | es_ES |
dc.subject.mesh | Cricetulus | es_ES |
dc.subject.mesh | Fibroblasts | es_ES |
dc.subject.mesh | GTP-Binding Protein alpha Subunits, Gq-G11 | es_ES |
dc.subject.mesh | HEK293 Cells | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Lysosomes | es_ES |
dc.subject.mesh | Male | es_ES |
dc.subject.mesh | Mechanistic Target of Rapamycin Complex 1 | es_ES |
dc.subject.mesh | Mice | es_ES |
dc.subject.mesh | Models, Biological | es_ES |
dc.subject.mesh | Phenotype | es_ES |
dc.subject.mesh | Protein Binding | es_ES |
dc.subject.mesh | Protein Domains | es_ES |
dc.subject.mesh | Rats, Wistar | es_ES |
dc.subject.mesh | Regulatory-Associated Protein of mTOR | es_ES |
dc.subject.mesh | Sequestosome-1 Protein | es_ES |
dc.title | Gαq activation modulates autophagy by promoting mTORC1 signaling. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución-NoComercial-CompartirIgual 4.0 Internacional | * |
dc.identifier.pubmedID | 34315875 | es_ES |
dc.format.volume | 12 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 4540 | es_ES |
dc.identifier.doi | 10.1038/s41467-021-24811-4 | es_ES |
dc.contributor.funder | Ministerio de Economía, Industria y Competitividad (España) | |
dc.contributor.funder | Instituto de Salud Carlos III | |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2041-1723 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1038/s41467-021-24811-4. | es_ES |
dc.identifier.journal | Nature communications | es_ES |
dc.repisalud.institucion | CNIO | es_ES |
dc.repisalud.orgCNIO | CNIO::Grupos de investigación::Grupo de Biología Computacional Estructural | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/SAF2017-84125-R | es_ES |
dc.relation.projectFIS | info:eu-repo/grantAgreement/ES/PI18/01662 | es_ES |