{"date_updated":"2024-04-23T22:30:29Z","ec_funded":1,"isi":1,"quality_controlled":"1","abstract":[{"lang":"eng","text":"The synaptic connection from medial habenula (MHb) to interpeduncular nucleus (IPN) is critical for emotion-related behaviors and uniquely expresses R-type Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates or inhibits transmitter release from MHb terminals depending on the IPN subnucleus, but the role of KCTDs is unknown. We therefore examined the localization and function of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3 currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b, and Cav2.3 co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3 with KCTDs therefore scales synaptic strength independent of GBR activation."}],"publisher":"eLife Sciences Publications","title":"GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals","intvolume":"        10","publication_status":"published","external_id":{"isi":["000651761700001"]},"language":[{"iso":"eng"}],"date_published":"2021-04-29T00:00:00Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_created":"2021-05-30T22:01:23Z","oa_version":"Published Version","acknowledgement":"We are grateful to Akari Hagiwara and Toshihisa Ohtsuka for CAST antibody, and Masahiko Watanabe for neurexin antibody. We thank David Adams for kindly providing the stable Cav2.3 cell line. Cav2.3 KO mice were kindly provided by Tsutomu Tanabe. This project has received funding from the European Research Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research and innovation programme (ERC grant agreement no. 694539 to Ryuichi Shigemoto, no. 692692 to Peter Jonas, and the Marie Skłodowska-Curie grant agreement no. 665385 to Cihan Önal), the Swiss National Science Foundation Grant 31003A-172881 to Bernhard Bettler and Deutsche Forschungsgemeinschaft (For 2143) and BIOSS-2 to Akos Kulik.","year":"2021","month":"04","article_type":"original","publication_identifier":{"eissn":["2050-084X"]},"related_material":{"link":[{"relation":"earlier_version","url":"https://doi.org/10.1101/2020.04.16.045112"}],"record":[{"status":"public","relation":"dissertation_contains","id":"9562"}]},"file_date_updated":"2021-05-31T09:43:09Z","_id":"9437","doi":"10.7554/ELIFE.68274","day":"29","author":[{"orcid":"0000-0003-0863-4481","last_name":"Bhandari","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","first_name":"Pradeep","full_name":"Bhandari, Pradeep"},{"full_name":"Vandael, David H","first_name":"David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7577-1676","last_name":"Vandael"},{"last_name":"Fernández-Fernández","first_name":"Diego","full_name":"Fernández-Fernández, Diego"},{"last_name":"Fritzius","first_name":"Thorsten","full_name":"Fritzius, Thorsten"},{"first_name":"David","full_name":"Kleindienst, David","last_name":"Kleindienst","id":"42E121A4-F248-11E8-B48F-1D18A9856A87"},{"id":"4659D740-F248-11E8-B48F-1D18A9856A87","last_name":"Önal","orcid":"0000-0002-2771-2011","full_name":"Önal, Hüseyin C","first_name":"Hüseyin C"},{"full_name":"Montanaro-Punzengruber, Jacqueline-Claire","first_name":"Jacqueline-Claire","id":"3786AB44-F248-11E8-B48F-1D18A9856A87","last_name":"Montanaro-Punzengruber"},{"full_name":"Gassmann, Martin","first_name":"Martin","last_name":"Gassmann"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M","first_name":"Peter M"},{"last_name":"Kulik","full_name":"Kulik, Akos","first_name":"Akos"},{"last_name":"Bettler","full_name":"Bettler, Bernhard","first_name":"Bernhard"},{"first_name":"Ryuichi","full_name":"Shigemoto, Ryuichi","last_name":"Shigemoto","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Koppensteiner, Peter","first_name":"Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","last_name":"Koppensteiner","orcid":"0000-0002-3509-1948"}],"article_processing_charge":"No","file":[{"date_created":"2021-05-31T09:43:09Z","checksum":"6ebcb79999f889766f7cd79ee134ad28","content_type":"application/pdf","file_id":"9440","success":1,"file_size":8174719,"relation":"main_file","creator":"cziletti","access_level":"open_access","file_name":"2021_eLife_Bhandari.pdf","date_updated":"2021-05-31T09:43:09Z"}],"oa":1,"tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"citation":{"apa":"Bhandari, P., Vandael, D. H., Fernández-Fernández, D., Fritzius, T., Kleindienst, D., Önal, H. C., … Koppensteiner, P. (2021). GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/ELIFE.68274\">https://doi.org/10.7554/ELIFE.68274</a>","short":"P. Bhandari, D.H. Vandael, D. Fernández-Fernández, T. Fritzius, D. Kleindienst, H.C. Önal, J.-C. Montanaro-Punzengruber, M. Gassmann, P.M. Jonas, A. Kulik, B. Bettler, R. Shigemoto, P. Koppensteiner, ELife 10 (2021).","chicago":"Bhandari, Pradeep, David H Vandael, Diego Fernández-Fernández, Thorsten Fritzius, David Kleindienst, Hüseyin C Önal, Jacqueline-Claire Montanaro-Punzengruber, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/ELIFE.68274\">https://doi.org/10.7554/ELIFE.68274</a>.","mla":"Bhandari, Pradeep, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” <i>ELife</i>, vol. 10, e68274, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/ELIFE.68274\">10.7554/ELIFE.68274</a>.","ieee":"P. Bhandari <i>et al.</i>, “GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","ista":"Bhandari P, Vandael DH, Fernández-Fernández D, Fritzius T, Kleindienst D, Önal HC, Montanaro-Punzengruber J-C, Gassmann M, Jonas PM, Kulik A, Bettler B, Shigemoto R, Koppensteiner P. 2021. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. eLife. 10, e68274.","ama":"Bhandari P, Vandael DH, Fernández-Fernández D, et al. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/ELIFE.68274\">10.7554/ELIFE.68274</a>"},"volume":10,"scopus_import":"1","project":[{"call_identifier":"H2020","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","grant_number":"694539"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"International IST Doctoral Program"}],"publication":"eLife","article_number":"e68274","has_accepted_license":"1","status":"public","type":"journal_article","department":[{"_id":"RySh"},{"_id":"PeJo"}],"ddc":["570"]}