{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T15:25:08Z","timestamp":1781105108233,"version":"3.54.1"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"49","license":[{"start":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T00:00:00Z","timestamp":1732665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100030692","name":"HHS | NIH | NIDA | Intramural Research Program","doi-asserted-by":"publisher","award":["Z01-ES101643"],"award-info":[{"award-number":["Z01-ES101643"]}],"id":[{"id":"10.13039\/100030692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF2020R1I1A1A01053066"],"award-info":[{"award-number":["NRF2020R1I1A1A01053066"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2018R1A5A2025964"],"award-info":[{"award-number":["2018R1A5A2025964"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018749","name":"Korea Brain Research Institute","doi-asserted-by":"publisher","award":["23-BR-02-03"],"award-info":[{"award-number":["23-BR-02-03"]}],"id":[{"id":"10.13039\/100018749","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,12,3]]},"abstract":"<jats:p>\n                    <jats:italic>GNAO1<\/jats:italic>\n                    encodes the alpha subunit of the heterotrimeric Go protein. Despite being the most abundant G protein at synapses, the role of Go in the brain remains unclear, primarily because of the high mortality associated with developmental and epileptic encephalopathy (DEE) 17 in\n                    <jats:italic>Gnao1<\/jats:italic>\n                    mutated animals. Here, we conducted proteomic analyses with a brain synaptosomal fraction to investigate the Go-interactome and then generated a non-DEE model using\n                    <jats:italic>\n                      Gli1\n                      <jats:sup>CreERT2<\/jats:sup>\n                    <\/jats:italic>\n                    mice to selectively knockout (KO) the presynaptic G\u03b1o within cerebellum. Our findings revealed that G\u03b1o interacts with multiple proteins involved in neurotransmitter release, as well as cannabinoid receptor type 1 (CB1R), a key Gi\/o-coupled receptor in presynaptic terminals. In\n                    <jats:italic>Gnao1<\/jats:italic>\n                    KO mice, synapse formation was reduced in the cerebellum with a concomitant reduction in depolarization-induced suppression of excitation, a manifestation of CB1R-mediated synaptic plasticity found in the cerebellum. These mice displayed motor deficits in rotarod, grip strength, gait, and beam balance tests. Our results suggest that Go plays a critical role in regulating neurotransmitter releases at the presynaptic terminals and its absence in the entire brain may contribute to DEE pathogenesis. This study also provides valuable insights into the signaling pathways in the brain from a Go-dependent perspective.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2409773121","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T12:13:52Z","timestamp":1732709632000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1,"title":["CB1R activates the epilepsy-associated protein Go to regulate neurotransmitter release and synaptic plasticity in the cerebellum"],"prefix":"10.1073","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4399-5792","authenticated-orcid":false,"given":"Jung-Mi","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Anatomy, Ajou University School of Medicine, Suwon 16499, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakshya","family":"Acharya","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Ajou University School of Medicine, Suwon 16499, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Lim","family":"Cha","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Ajou University School of Medicine, Suwon 16499, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang-Wook","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Ajou University School of Medicine, Suwon 16499, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9162-848X","authenticated-orcid":false,"given":"Jewoo","family":"Seo","sequence":"additional","affiliation":[{"name":"Department Physiology, Seoul National University College of Medicine, Seoul 03080, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine, Korea University, Seoul 02841, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4090-3832","authenticated-orcid":false,"given":"Jong Hyuk","family":"Yoon","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Research Group, Korea Brain Research Institute, Daegu 41062, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da-Young","family":"Chang","sequence":"additional","affiliation":[{"name":"Research Center, CELLeBRAIN Co., Ltd., Suwon 16681, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Soo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Ajou University School of Medicine, Suwon 16499, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8931-3713","authenticated-orcid":false,"given":"Sang Jeong","family":"Kim","sequence":"additional","affiliation":[{"name":"Department Physiology, Seoul National University College of Medicine, Seoul 03080, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0775-8661","authenticated-orcid":false,"given":"Lutz","family":"Birnbaumer","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Research, School of Biomedical Sciences, Catholic University of Argentina, Buenos Aires C1107AFF, Argentina"},{"name":"Signal Transduction Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haeyoung","family":"Suh-Kim","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Ajou University School of Medicine, Suwon 16499, South Korea"},{"name":"Research Center, CELLeBRAIN Co., Ltd., Suwon 16681, South Korea"},{"name":"Department of Biomedical Sciences, Graduate School, Ajou University School of Medicine, Suwon 16499, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2024,11,27]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.07.014"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00335-014-9509-z"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1177\/0883073816666474"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000143"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2015.92"},{"key":"e_1_3_4_6_2","volume-title":"GeneReviews(R)","author":"Briere L.","year":"1993","unstructured":"L. Briere, M. Thiel, D. A. Sweetser, A. Koy, E. Axeen, \u201cGNAO1-related disorder\u201d in GeneReviews(R), M. P. Adam , Eds. (University of Washington, Seattle, WA, 1993\u20132024)."},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)85162-1"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200800767"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4160"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.07.015"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.5.1727"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.6.3269"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2020.00108"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4872-05.2006"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3167-14.2015"},{"key":"e_1_3_4_16_2","first-page":"1000","article-title":"Activation of cannabinoid receptors in rat brain by WIN 55212\u20132 produces coupling to multiple G protein alpha-subunits with different potencies","volume":"57","author":"Prather P. L.","year":"2000","unstructured":"P. L. Prather, N. A. Martin, C. S. Breivogel, S. R. Childers, Activation of cannabinoid receptors in rat brain by WIN 55212\u20132 produces coupling to multiple G protein alpha-subunits with different potencies. Mol. Pharmacol. 57, 1000\u20131010 (2000).","journal-title":"Mol. Pharmacol."},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2018.08.012"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1347957"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8327893"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.5607\/en21017"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1107770108"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-019-0477-9"},{"key":"e_1_3_4_23_2","author":"Altman J.","year":"1996","unstructured":"J. Altman, S. A. Bayer, Development of the Cerebellar System: In Relation to Its Evolution, Structure, and Functions (CRC Press, Boca Raton, FL, 1996).","journal-title":"Development of the Cerebellar System: In Relation to Its Evolution, Structure, and Functions"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1511513113"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2012.00090"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1177\/1073858406296716"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-23810-0_39"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2300585120"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-07-02460.2002"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.09.020"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00980.2010"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-39632-5.00027-X"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00720.2020"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2012.01.009"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-019-0497-2"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2017.00003"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2012.05.017"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2009.12.061"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2000877"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M104806200"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.16.10685"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb.2009.27"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.09.167"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0609392103"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.108718"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-016-0384-x"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.crmeth.2022.100275"},{"key":"e_1_3_4_48_2","first-page":"24","article-title":"Mice with GNAO1 R209H movement disorder variant display hyperlocomotion alleviated by risperidone","volume":"373","author":"Larrivee C. L.","year":"2020","unstructured":"C. L. Larrivee , Mice with GNAO1 R209H movement disorder variant display hyperlocomotion alleviated by risperidone. J. Pharmacol. Exp. Ther. 373, 24\u201333 (2020).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9030757"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1159\/000186688"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2019.00089"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a011148"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17886-y"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.2409773121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T12:15:37Z","timestamp":1732709737000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/10.1073\/pnas.2409773121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,27]]},"references-count":53,"journal-issue":{"issue":"49","published-print":{"date-parts":[[2024,12,3]]}},"alternative-id":["10.1073\/pnas.2409773121"],"URL":"https:\/\/doi.org\/10.1073\/pnas.2409773121","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,27]]},"assertion":[{"value":"2024-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-10-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-11-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e2409773121"}}