---
_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. eLife.
2021;10. doi:10.7554/ELIFE.68274
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. ELife.
eLife Sciences Publications. https://doi.org/10.7554/ELIFE.68274
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.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/ELIFE.68274.
ieee: P. Bhandari et al., “GABAB receptor auxiliary subunits modulate Cav2.3-mediated
release from medial habenula terminals,” eLife, 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.” ELife, vol. 10, e68274, eLife
Sciences Publications, 2021, doi:10.7554/ELIFE.68274.
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: 2024-03-28T23:30:31Z
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
file_id: '9440'
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'
...