{"oa_version":"Published Version","external_id":{"pmid":["38568976"]},"has_accepted_license":"1","file_date_updated":"2024-04-23T06:53:14Z","date_published":"2024-04-09T00:00:00Z","department":[{"_id":"LoSw"}],"oa":1,"acknowledgement":"We thank all members of the Spitzer laboratory for discussions and critical feedback; K. Marek for discussions of acknowledgment signals; I. Gregor and R. Aricescu for discussions of receptor pharmacology and transsynaptic bridges; C. Kintner for advice on Xenopus blastomere lineage; A. Ray and E. Park for guidance on miniature analysis; A. Glavis- Bloom, S.U. Choi, S. Atkins, M. Gupta, and S. Malladi for technical assistance; and D. K. Berg and L. R. Squire for comments on the manuscript. This work was supported by NSF 2051555 and the Overland Foundation. Microscopy for five- channel imaging utilized the UCSD School of Medicine Microscopy Core, supported by NIH grant NS047101.","language":[{"iso":"eng"}],"article_number":"e2318041121","status":"public","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","file":[{"date_created":"2024-04-23T06:53:14Z","success":1,"file_name":"2024_PNAS_Godavarthi.pdf","content_type":"application/pdf","file_id":"15340","date_updated":"2024-04-23T06:53:14Z","relation":"main_file","access_level":"open_access","file_size":16187094,"creator":"dernst","checksum":"f3b4ffad4ef3d1c443414edf0cd2392c"}],"tmp":{"short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"eissn":["1091-6490"]},"type":"journal_article","citation":{"chicago":"Godavarthi, Swetha K., Masaki Hiramoto, Yuri Ignatyev, Jacqueline B. Levin, Hui Quan Li, Marta Pratelli, Jennifer Borchardt, et al. “Postsynaptic Receptors Regulate Presynaptic Transmitter Stability through Transsynaptic Bridges.” PNAS. Proceedings of the National Academy of Sciences, 2024. https://doi.org/10.1073/pnas.2318041121.","apa":"Godavarthi, S. K., Hiramoto, M., Ignatyev, Y., Levin, J. B., Li, H. Q., Pratelli, M., … Spitzer, N. C. (2024). Postsynaptic receptors regulate presynaptic transmitter stability through transsynaptic bridges. PNAS. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.2318041121","short":"S.K. Godavarthi, M. Hiramoto, Y. Ignatyev, J.B. Levin, H.Q. Li, M. Pratelli, J. Borchardt, C. Czajkowski, L.N. Borodinsky, L.B. Sweeney, H.T. Cline, N.C. Spitzer, PNAS 121 (2024).","ieee":"S. K. Godavarthi et al., “Postsynaptic receptors regulate presynaptic transmitter stability through transsynaptic bridges,” PNAS, vol. 121, no. 15. Proceedings of the National Academy of Sciences, 2024.","mla":"Godavarthi, Swetha K., et al. “Postsynaptic Receptors Regulate Presynaptic Transmitter Stability through Transsynaptic Bridges.” PNAS, vol. 121, no. 15, e2318041121, Proceedings of the National Academy of Sciences, 2024, doi:10.1073/pnas.2318041121.","ama":"Godavarthi SK, Hiramoto M, Ignatyev Y, et al. Postsynaptic receptors regulate presynaptic transmitter stability through transsynaptic bridges. PNAS. 2024;121(15). doi:10.1073/pnas.2318041121","ista":"Godavarthi SK, Hiramoto M, Ignatyev Y, Levin JB, Li HQ, Pratelli M, Borchardt J, Czajkowski C, Borodinsky LN, Sweeney LB, Cline HT, Spitzer NC. 2024. Postsynaptic receptors regulate presynaptic transmitter stability through transsynaptic bridges. PNAS. 121(15), e2318041121."},"ddc":["570"],"volume":121,"doi":"10.1073/pnas.2318041121","issue":"15","publisher":"Proceedings of the National Academy of Sciences","scopus_import":"1","day":"09","pmid":1,"month":"04","intvolume":" 121","article_processing_charge":"Yes (in subscription journal)","publication_status":"published","quality_controlled":"1","date_created":"2024-04-21T22:00:53Z","_id":"15335","date_updated":"2024-04-23T06:56:09Z","article_type":"original","publication":"PNAS","year":"2024","title":"Postsynaptic receptors regulate presynaptic transmitter stability through transsynaptic bridges","abstract":[{"text":"Stable matching of neurotransmitters with their receptors is fundamental to synapse function and reliable communication in neural circuits. Presynaptic neurotransmitters regulate the stabilization of postsynaptic transmitter receptors. Whether postsynaptic receptors regulate stabilization of presynaptic transmitters has received less attention. Here, we show that blockade of endogenous postsynaptic acetylcholine receptors (AChR) at the neuromuscular junction destabilizes the cholinergic phenotype in motor neurons and stabilizes an earlier, developmentally transient glutamatergic phenotype. Further, expression of exogenous postsynaptic gamma-aminobutyric acid type A receptors (GABAA receptors) in muscle cells stabilizes an earlier, developmentally transient GABAergic motor neuron phenotype. Both AChR and GABAA receptors are linked to presynaptic neurons through transsynaptic bridges. Knockdown of specific components of these transsynaptic bridges prevents stabilization of the cholinergic or GABAergic phenotypes. Bidirectional communication can enforce a match between transmitter and receptor and ensure the fidelity of synaptic transmission. Our findings suggest a potential role of dysfunctional transmitter receptors in neurological disorders that involve the loss of the presynaptic transmitter.","lang":"eng"}],"author":[{"first_name":"Swetha K.","full_name":"Godavarthi, Swetha K.","last_name":"Godavarthi"},{"full_name":"Hiramoto, Masaki","first_name":"Masaki","last_name":"Hiramoto"},{"full_name":"Ignatyev, Yuri","first_name":"Yuri","last_name":"Ignatyev"},{"first_name":"Jacqueline B.","full_name":"Levin, Jacqueline B.","last_name":"Levin"},{"last_name":"Li","full_name":"Li, Hui Quan","first_name":"Hui Quan"},{"last_name":"Pratelli","first_name":"Marta","full_name":"Pratelli, Marta"},{"first_name":"Jennifer","full_name":"Borchardt, Jennifer","last_name":"Borchardt"},{"first_name":"Cynthia","full_name":"Czajkowski, Cynthia","last_name":"Czajkowski"},{"last_name":"Borodinsky","full_name":"Borodinsky, Laura N.","first_name":"Laura N."},{"orcid":"0000-0001-9242-5601","last_name":"Sweeney","full_name":"Sweeney, Lora Beatrice Jaeger","id":"56BE8254-C4F0-11E9-8E45-0B23E6697425","first_name":"Lora Beatrice Jaeger"},{"last_name":"Cline","first_name":"Hollis T.","full_name":"Cline, Hollis T."},{"last_name":"Spitzer","full_name":"Spitzer, Nicholas C.","first_name":"Nicholas C."}]}