---
_id: '9437'
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.
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.
article_number: e68274
article_processing_charge: No
article_type: original
author:
- first_name: Pradeep
  full_name: Bhandari, Pradeep
  id: 45EDD1BC-F248-11E8-B48F-1D18A9856A87
  last_name: Bhandari
  orcid: 0000-0003-0863-4481
- first_name: David H
  full_name: Vandael, David H
  id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
  last_name: Vandael
  orcid: 0000-0001-7577-1676
- first_name: Diego
  full_name: Fernández-Fernández, Diego
  last_name: Fernández-Fernández
- first_name: Thorsten
  full_name: Fritzius, Thorsten
  last_name: Fritzius
- first_name: David
  full_name: Kleindienst, David
  id: 42E121A4-F248-11E8-B48F-1D18A9856A87
  last_name: Kleindienst
- first_name: Hüseyin C
  full_name: Önal, Hüseyin C
  id: 4659D740-F248-11E8-B48F-1D18A9856A87
  last_name: Önal
  orcid: 0000-0002-2771-2011
- first_name: Jacqueline-Claire
  full_name: Montanaro-Punzengruber, Jacqueline-Claire
  id: 3786AB44-F248-11E8-B48F-1D18A9856A87
  last_name: Montanaro-Punzengruber
- first_name: Martin
  full_name: Gassmann, Martin
  last_name: Gassmann
- first_name: Peter M
  full_name: Jonas, Peter M
  id: 353C1B58-F248-11E8-B48F-1D18A9856A87
  last_name: Jonas
  orcid: 0000-0001-5001-4804
- first_name: Akos
  full_name: Kulik, Akos
  last_name: Kulik
- first_name: Bernhard
  full_name: Bettler, Bernhard
  last_name: Bettler
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
citation:
  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>
  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>
  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>.
  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.
  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>.
  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).
date_created: 2021-05-30T22:01:23Z
date_published: 2021-04-29T00:00:00Z
date_updated: 2024-03-25T23:30:16Z
day: '29'
ddc:
- '570'
department:
- _id: RySh
- _id: PeJo
doi: 10.7554/ELIFE.68274
ec_funded: 1
external_id:
  isi:
  - '000651761700001'
file:
- access_level: open_access
  checksum: 6ebcb79999f889766f7cd79ee134ad28
  content_type: application/pdf
  creator: cziletti
  date_created: 2021-05-31T09:43:09Z
  date_updated: 2021-05-31T09:43:09Z
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  file_name: 2021_eLife_Bhandari.pdf
  file_size: 8174719
  relation: main_file
  success: 1
file_date_updated: 2021-05-31T09:43:09Z
has_accepted_license: '1'
intvolume: '        10'
isi: 1
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '04'
oa: 1
oa_version: Published Version
project:
- _id: 25CA28EA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '694539'
  name: 'In situ analysis of single channel subunit composition in neurons: physiological
    implication in synaptic plasticity and behaviour'
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '692692'
  name: Biophysics and circuit function of a giant cortical glumatergic synapse
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
  call_identifier: H2020
  grant_number: '665385'
  name: International IST Doctoral Program
publication: eLife
publication_identifier:
  eissn:
  - 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
related_material:
  link:
  - relation: earlier_version
    url: https://doi.org/10.1101/2020.04.16.045112
  record:
  - id: '9562'
    relation: dissertation_contains
    status: public
scopus_import: '1'
status: public
title: GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial
  habenula terminals
tmp:
  image: /images/cc_by.png
  legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
  name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
  short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 10
year: '2021'
...