[{"file_date_updated":"2021-11-18T07:02:02Z","article_number":"e71575","author":[{"full_name":"Conde-Dusman, María J","last_name":"Conde-Dusman","first_name":"María J"},{"last_name":"Dey","first_name":"Partha N","full_name":"Dey, Partha N"},{"first_name":"Óscar","last_name":"Elía-Zudaire","full_name":"Elía-Zudaire, Óscar"},{"id":"33D1B084-F248-11E8-B48F-1D18A9856A87","first_name":"Luis E","last_name":"Garcia Rabaneda","full_name":"Garcia Rabaneda, Luis E"},{"first_name":"Carmen","last_name":"García-Lira","full_name":"García-Lira, Carmen"},{"full_name":"Grand, Teddy","first_name":"Teddy","last_name":"Grand"},{"full_name":"Briz, Victor","first_name":"Victor","last_name":"Briz"},{"last_name":"Velasco","first_name":"Eric R","full_name":"Velasco, Eric R"},{"full_name":"Andero Galí, Raül","last_name":"Andero Galí","first_name":"Raül"},{"full_name":"Niñerola, Sergio","last_name":"Niñerola","first_name":"Sergio"},{"full_name":"Barco, Angel","last_name":"Barco","first_name":"Angel"},{"full_name":"Paoletti, Pierre","last_name":"Paoletti","first_name":"Pierre"},{"first_name":"John F","last_name":"Wesseling","full_name":"Wesseling, John F"},{"full_name":"Gardoni, Fabrizio","first_name":"Fabrizio","last_name":"Gardoni"},{"full_name":"Tavalin, Steven J","last_name":"Tavalin","first_name":"Steven J"},{"full_name":"Perez-Otaño, Isabel","last_name":"Perez-Otaño","first_name":"Isabel"}],"volume":10,"date_updated":"2023-08-14T11:50:50Z","date_created":"2021-11-18T06:59:45Z","acknowledgement":"We thank Stuart Lipton and Nobuki Nakanishi for providing the Grin3a knockout mice, Beverly Davidson for the AAV-caRheb, Jose Esteban for help with behavioral and biochemical experiments, and Noelia Campillo, Rebeca Martínez-Turrillas, and Ana Navarro for expert technical help. Work was funded by the UTE project CIMA; fellowships from the Fundación Tatiana Pérez de Guzmán el Bueno, FEBS, and IBRO (to M.J.C.D.), Generalitat Valenciana (to O.E.-Z.), Juan de la Cierva (to L.G.R.), FPI-MINECO (to E.R.V., to S.N.) and Intertalentum postdoctoral program (to V.B.); ANR (GluBrain3A) and ERC Advanced Grants (#693021) (to P.P.); Ramón y Cajal program RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077 FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637) and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R), Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence Awards (SEV-2013-0317, SEV-2017-0723).","year":"2021","department":[{"_id":"GaNo"}],"publisher":"eLife Sciences Publications","publication_status":"published","publication_identifier":{"issn":["2050-084X"]},"month":"11","doi":"10.7554/elife.71575","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000720945900001"]},"quality_controlled":"1","isi":1,"abstract":[{"lang":"eng","text":"De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement."}],"type":"journal_article","file":[{"date_updated":"2021-11-18T07:02:02Z","date_created":"2021-11-18T07:02:02Z","checksum":"59318e9e41507cec83c2f4070e6ad540","success":1,"relation":"main_file","file_id":"10302","content_type":"application/pdf","file_size":2477302,"creator":"lgarciar","file_name":"elife-71575-v1.pdf","access_level":"open_access"}],"oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"10301","intvolume":" 10","status":"public","title":"Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly","ddc":["570"],"article_processing_charge":"No","has_accepted_license":"1","day":"17","keyword":["general immunology and microbiology","general biochemistry","genetics and molecular biology","general medicine","general neuroscience"],"date_published":"2021-11-17T00:00:00Z","citation":{"mla":"Conde-Dusman, María J., et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” ELife, vol. 10, e71575, eLife Sciences Publications, 2021, doi:10.7554/elife.71575.","short":"M.J. Conde-Dusman, P.N. Dey, Ó. Elía-Zudaire, L.E. Garcia Rabaneda, C. García-Lira, T. Grand, V. Briz, E.R. Velasco, R. Andero Galí, S. Niñerola, A. Barco, P. Paoletti, J.F. Wesseling, F. Gardoni, S.J. Tavalin, I. Perez-Otaño, ELife 10 (2021).","chicago":"Conde-Dusman, María J, Partha N Dey, Óscar Elía-Zudaire, Luis E Garcia Rabaneda, Carmen García-Lira, Teddy Grand, Victor Briz, et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.71575.","ama":"Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, et al. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife. 2021;10. doi:10.7554/elife.71575","ista":"Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, Garcia Rabaneda LE, García-Lira C, Grand T, Briz V, Velasco ER, Andero Galí R, Niñerola S, Barco A, Paoletti P, Wesseling JF, Gardoni F, Tavalin SJ, Perez-Otaño I. 2021. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife. 10, e71575.","ieee":"M. J. Conde-Dusman et al., “Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly,” eLife, vol. 10. eLife Sciences Publications, 2021.","apa":"Conde-Dusman, M. J., Dey, P. N., Elía-Zudaire, Ó., Garcia Rabaneda, L. E., García-Lira, C., Grand, T., … Perez-Otaño, I. (2021). Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.71575"},"publication":"eLife","article_type":"original"},{"doi":"10.1016/j.tins.2020.05.004","language":[{"iso":"eng"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["32507511"],"isi":["000553090600008"]},"oa":1,"project":[{"_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020"}],"quality_controlled":"1","isi":1,"publication_identifier":{"issn":["01662236"],"eissn":["1878108X"]},"month":"08","author":[{"full_name":"Parenti, Ilaria","id":"D93538B0-5B71-11E9-AC62-02EBE5697425","first_name":"Ilaria","last_name":"Parenti"},{"full_name":"Garcia Rabaneda, Luis E","id":"33D1B084-F248-11E8-B48F-1D18A9856A87","first_name":"Luis E","last_name":"Garcia Rabaneda"},{"last_name":"Schön","first_name":"Hanna","id":"C8E17EDC-D7AA-11E9-B7B7-45ECE5697425","full_name":"Schön, Hanna"},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia"}],"volume":43,"date_updated":"2023-08-21T08:25:31Z","date_created":"2020-06-14T22:00:49Z","pmid":1,"year":"2020","acknowledgement":"We wish to thank Jasmin Morandell for generously sharing Figure 2. This work was supported by the European Research Council Starting Grant (grant 715508 ) to G.N.","department":[{"_id":"GaNo"}],"publisher":"Elsevier","publication_status":"published","ec_funded":1,"file_date_updated":"2020-11-25T09:43:40Z","date_published":"2020-08-01T00:00:00Z","citation":{"chicago":"Parenti, Ilaria, Luis E Garcia Rabaneda, Hanna Schön, and Gaia Novarino. “Neurodevelopmental Disorders: From Genetics to Functional Pathways.” Trends in Neurosciences. Elsevier, 2020. https://doi.org/10.1016/j.tins.2020.05.004.","mla":"Parenti, Ilaria, et al. “Neurodevelopmental Disorders: From Genetics to Functional Pathways.” Trends in Neurosciences, vol. 43, no. 8, Elsevier, 2020, pp. 608–21, doi:10.1016/j.tins.2020.05.004.","short":"I. Parenti, L.E. Garcia Rabaneda, H. Schön, G. Novarino, Trends in Neurosciences 43 (2020) 608–621.","ista":"Parenti I, Garcia Rabaneda LE, Schön H, Novarino G. 2020. Neurodevelopmental disorders: From genetics to functional pathways. Trends in Neurosciences. 43(8), 608–621.","ieee":"I. Parenti, L. E. Garcia Rabaneda, H. Schön, and G. Novarino, “Neurodevelopmental disorders: From genetics to functional pathways,” Trends in Neurosciences, vol. 43, no. 8. Elsevier, pp. 608–621, 2020.","apa":"Parenti, I., Garcia Rabaneda, L. E., Schön, H., & Novarino, G. (2020). Neurodevelopmental disorders: From genetics to functional pathways. Trends in Neurosciences. Elsevier. https://doi.org/10.1016/j.tins.2020.05.004","ama":"Parenti I, Garcia Rabaneda LE, Schön H, Novarino G. Neurodevelopmental disorders: From genetics to functional pathways. Trends in Neurosciences. 2020;43(8):608-621. doi:10.1016/j.tins.2020.05.004"},"publication":"Trends in Neurosciences","page":"608-621","article_type":"original","article_processing_charge":"No","has_accepted_license":"1","day":"01","scopus_import":"1","file":[{"date_updated":"2020-11-25T09:43:40Z","date_created":"2020-11-25T09:43:40Z","checksum":"67db0251b1d415ae59005f876fcf9e34","success":1,"relation":"main_file","file_id":"8805","file_size":1439550,"content_type":"application/pdf","creator":"dernst","file_name":"2020_TrendsNeuroscience_Parenti.pdf","access_level":"open_access"}],"oa_version":"Published Version","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"7957","intvolume":" 43","status":"public","ddc":["570"],"title":"Neurodevelopmental disorders: From genetics to functional pathways","issue":"8","abstract":[{"lang":"eng","text":"Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain development and function and are characterized by wide genetic and clinical variability. In this review, we discuss the multiple factors that influence the clinical presentation of NDDs, with particular attention to gene vulnerability, mutational load, and the two-hit model. Despite the complex architecture of\r\nmutational events associated with NDDs, the various proteins involved appear to converge on common pathways, such as synaptic plasticity/function, chromatin remodelers and the mammalian target of rapamycin (mTOR) pathway. A thorough understanding of the mechanisms behind these pathways will hopefully lead to the identification of candidates that could be targeted for treatment approaches."}],"type":"journal_article"}]