---
_id: '12875'
abstract:
- lang: eng
  text: The superior colliculus (SC) in the mammalian midbrain is essential for multisensory
    integration and is composed of a rich diversity of excitatory and inhibitory neurons
    and glia. However, the developmental principles directing the generation of SC
    cell-type diversity are not understood. Here, we pursued systematic cell lineage
    tracing in silico and in vivo, preserving full spatial information, using genetic
    mosaic analysis with double markers (MADM)-based clonal analysis with single-cell
    sequencing (MADM-CloneSeq). The analysis of clonally related cell lineages revealed
    that radial glial progenitors (RGPs) in SC are exceptionally multipotent. Individual
    resident RGPs have the capacity to produce all excitatory and inhibitory SC neuron
    types, even at the stage of terminal division. While individual clonal units show
    no pre-defined cellular composition, the establishment of appropriate relative
    proportions of distinct neuronal types occurs in a PTEN-dependent manner. Collectively,
    our findings provide an inaugural framework at the single-RGP/-cell level of the
    mammalian SC ontogeny.
acknowledged_ssus:
- _id: Bio
- _id: M-Shop
- _id: LifeSc
- _id: PreCl
acknowledgement: "We thank Liqun Luo for his continued support, for providing essential
  resources for generating Fzd10-CreER mice which were generated in his laboratory,
  and for comments on the manuscript; W. Zhong for providing Nestin-Cre transgenic
  mouse line for this study; A. Heger for mouse colony management; R. Beattie and
  T. Asenov for designing and producing components of acute slice recovery chamber
  for MADM-CloneSeq experiments; and K. Leopold, J. Rodarte and N. Amberg for initial
  experiments, technical support and/or assistance. This study was supported by the
  Scientific Service Units (SSU) of IST Austria through resources provided by the
  Imaging & Optics Facility (IOF), Laboratory Support Facility (LSF), Miba Machine
  Shop, and Pre-clinical Facility (PCF). G.C. received funding from European Commission
  (IST plus postdoctoral fellowship). This work was supported by ISTA institutional\r\nfunds;
  the Austrian Science Fund Special Research Programmes (FWF SFB F78 Neuro Stem Modulation)
  to S.H. "
article_processing_charge: Yes (via OA deal)
article_type: comment
author:
- first_name: Giselle T
  full_name: Cheung, Giselle T
  id: 471195F6-F248-11E8-B48F-1D18A9856A87
  last_name: Cheung
  orcid: 0000-0001-8457-2572
- first_name: Florian
  full_name: Pauler, Florian
  id: 48EA0138-F248-11E8-B48F-1D18A9856A87
  last_name: Pauler
  orcid: 0000-0002-7462-0048
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: Thomas
  full_name: Krausgruber, Thomas
  last_name: Krausgruber
- first_name: Carmen
  full_name: Streicher, Carmen
  id: 36BCB99C-F248-11E8-B48F-1D18A9856A87
  last_name: Streicher
- first_name: Martin
  full_name: Schrammel, Martin
  id: f13e7cae-e8bd-11ed-841a-96dedf69f46d
  last_name: Schrammel
- first_name: Natalie Y
  full_name: Özgen, Natalie Y
  id: e68ece33-f6e0-11ea-865d-ae1031dcc090
  last_name: Özgen
- first_name: Alexis
  full_name: Ivec, Alexis
  id: 1d144691-e8be-11ed-9b33-bdd3077fad4c
  last_name: Ivec
- first_name: Christoph
  full_name: Bock, Christoph
  last_name: Bock
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Simon
  full_name: Hippenmeyer, Simon
  id: 37B36620-F248-11E8-B48F-1D18A9856A87
  last_name: Hippenmeyer
  orcid: 0000-0003-2279-1061
date_created: 2023-04-27T09:41:48Z
date_published: 2024-01-17T00:00:00Z
date_updated: 2025-05-14T09:39:37Z
day: '17'
ddc:
- '570'
department:
- _id: SiHi
- _id: RySh
doi: 10.1016/j.neuron.2023.11.009
external_id:
  pmid:
  - '38096816'
file:
- access_level: open_access
  checksum: 32b3788f7085cf44a84108d8faaff3ce
  content_type: application/pdf
  creator: dernst
  date_created: 2024-02-06T13:56:15Z
  date_updated: 2024-02-06T13:56:15Z
  file_id: '14944'
  file_name: 2024_Neuron_Cheung.pdf
  file_size: 5942467
  relation: main_file
  success: 1
file_date_updated: 2024-02-06T13:56:15Z
has_accepted_license: '1'
intvolume: '       112'
issue: '2'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 230-246.e11
pmid: 1
project:
- _id: 059F6AB4-7A3F-11EA-A408-12923DDC885E
  grant_number: F07805
  name: Molecular Mechanisms of Neural Stem Cell Lineage Progression
publication: Neuron
publication_identifier:
  eisbn:
  - '1234995621'
  issn:
  - 0896-6273
  issnl:
  - 1234-5678
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - description: News on ISTA Website
    relation: press_release
    url: https://ista.ac.at/en/news/the-pedigree-of-brain-cells/
scopus_import: '1'
status: public
title: Multipotent progenitors instruct ontogeny of the superior colliculus
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 112
year: '2024'
...
---
_id: '7551'
abstract:
- lang: eng
  text: Novelty facilitates formation of memories. The detection of novelty and storage
    of contextual memories are both mediated by the hippocampus, yet the mechanisms
    that link these two functions remain to be defined. Dentate granule cells (GCs)
    of the dorsal hippocampus fire upon novelty exposure forming engrams of contextual
    memory. However, their key excitatory inputs from the entorhinal cortex are not
    responsive to novelty and are insufficient to make dorsal GCs fire reliably. Here
    we uncover a powerful glutamatergic pathway to dorsal GCs from ventral hippocampal
    mossy cells (MCs) that relays novelty, and is necessary and sufficient for driving
    dorsal GCs activation. Furthermore, manipulation of ventral MCs activity bidirectionally
    regulates novelty-induced contextual memory acquisition. Our results show that
    ventral MCs activity controls memory formation through an intra-hippocampal interaction
    mechanism gated by novelty.
acknowledgement: We thank Peter Jonas and Peter Somogyi for critically reading the
  manuscript, Satoshi Kida for helpful discussion, Taijia Makinen for providing the
  Prox1-creERT2 mouse line, and Hiromu Yawo for the VAMP2-Venus construct. We also
  thank Vivek Jayaraman, Ph.D.; Rex A. Kerr, Ph.D.; Douglas S. Kim, Ph.D.; Loren L.
  Looger, Ph.D.; and Karel Svoboda, Ph.D. from the GENIE Project, Janelia Farm Research
  Campus, Howard Hughes Medical Institute for the viral constructs used for GCaMP6s
  expression. We also thank Jacqueline Montanaro, Vanessa Zheden, David Kleindienst,
  and Laura Burnett for technical assistance, as well as Robert Beattie for imaging
  assistance. This work was supported by a European Research Council Advanced Grant
  694539 to R.S.
article_processing_charge: No
article_type: original
author:
- first_name: Felipe A
  full_name: Fredes Tolorza, Felipe A
  id: 384825DA-F248-11E8-B48F-1D18A9856A87
  last_name: Fredes Tolorza
- first_name: Maria A
  full_name: Silva Sifuentes, Maria A
  id: 371B3D6E-F248-11E8-B48F-1D18A9856A87
  last_name: Silva Sifuentes
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
- first_name: Kenta
  full_name: Kobayashi, Kenta
  last_name: Kobayashi
- first_name: Maximilian A
  full_name: Jösch, Maximilian A
  id: 2BD278E6-F248-11E8-B48F-1D18A9856A87
  last_name: Jösch
  orcid: 0000-0002-3937-1330
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
citation:
  ama: Fredes Tolorza FA, Silva Sifuentes MA, Koppensteiner P, Kobayashi K, Jösch
    MA, Shigemoto R. Ventro-dorsal hippocampal pathway gates novelty-induced contextual
    memory formation. <i>Current Biology</i>. 2021;31(1):P25-38.E5. doi:<a href="https://doi.org/10.1016/j.cub.2020.09.074">10.1016/j.cub.2020.09.074</a>
  apa: Fredes Tolorza, F. A., Silva Sifuentes, M. A., Koppensteiner, P., Kobayashi,
    K., Jösch, M. A., &#38; Shigemoto, R. (2021). Ventro-dorsal hippocampal pathway
    gates novelty-induced contextual memory formation. <i>Current Biology</i>. Elsevier.
    <a href="https://doi.org/10.1016/j.cub.2020.09.074">https://doi.org/10.1016/j.cub.2020.09.074</a>
  chicago: Fredes Tolorza, Felipe A, Maria A Silva Sifuentes, Peter Koppensteiner,
    Kenta Kobayashi, Maximilian A Jösch, and Ryuichi Shigemoto. “Ventro-Dorsal Hippocampal
    Pathway Gates Novelty-Induced Contextual Memory Formation.” <i>Current Biology</i>.
    Elsevier, 2021. <a href="https://doi.org/10.1016/j.cub.2020.09.074">https://doi.org/10.1016/j.cub.2020.09.074</a>.
  ieee: F. A. Fredes Tolorza, M. A. Silva Sifuentes, P. Koppensteiner, K. Kobayashi,
    M. A. Jösch, and R. Shigemoto, “Ventro-dorsal hippocampal pathway gates novelty-induced
    contextual memory formation,” <i>Current Biology</i>, vol. 31, no. 1. Elsevier,
    p. P25–38.E5, 2021.
  ista: Fredes Tolorza FA, Silva Sifuentes MA, Koppensteiner P, Kobayashi K, Jösch
    MA, Shigemoto R. 2021. Ventro-dorsal hippocampal pathway gates novelty-induced
    contextual memory formation. Current Biology. 31(1), P25–38.E5.
  mla: Fredes Tolorza, Felipe A., et al. “Ventro-Dorsal Hippocampal Pathway Gates
    Novelty-Induced Contextual Memory Formation.” <i>Current Biology</i>, vol. 31,
    no. 1, Elsevier, 2021, p. P25–38.E5, doi:<a href="https://doi.org/10.1016/j.cub.2020.09.074">10.1016/j.cub.2020.09.074</a>.
  short: F.A. Fredes Tolorza, M.A. Silva Sifuentes, P. Koppensteiner, K. Kobayashi,
    M.A. Jösch, R. Shigemoto, Current Biology 31 (2021) P25–38.E5.
date_created: 2020-02-28T10:56:18Z
date_published: 2021-01-11T00:00:00Z
date_updated: 2023-08-04T10:47:11Z
day: '11'
ddc:
- '570'
department:
- _id: MaJö
- _id: RySh
doi: 10.1016/j.cub.2020.09.074
ec_funded: 1
external_id:
  isi:
  - '000614361000020'
file:
- access_level: open_access
  checksum: b7b9c8bc84a08befce365c675229a7d1
  content_type: application/pdf
  creator: dernst
  date_created: 2020-10-19T13:31:28Z
  date_updated: 2020-10-19T13:31:28Z
  file_id: '8678'
  file_name: 2021_CurrentBiology_Fredes.pdf
  file_size: 4915964
  relation: main_file
  success: 1
file_date_updated: 2020-10-19T13:31:28Z
has_accepted_license: '1'
intvolume: '        31'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: P25-38.E5
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'
publication: Current Biology
publication_status: published
publisher: Elsevier
quality_controlled: '1'
related_material:
  link:
  - description: News on IST Homepage
    relation: press_release
    url: https://ist.ac.at/en/news/remembering-novelty/
status: public
title: Ventro-dorsal hippocampal pathway gates novelty-induced contextual memory formation
tmp:
  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)
  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 31
year: '2021'
...
---
_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
  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
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'
...
---
_id: '10051'
abstract:
- lang: eng
  text: 'Rab-interacting molecule (RIM)-binding protein 2 (BP2) is a multidomain protein
    of the presynaptic active zone (AZ). By binding to RIM, bassoon (Bsn), and voltage-gated
    Ca2+ channels (CaV), it is considered to be a central organizer of the topography
    of CaV and release sites of synaptic vesicles (SVs) at the AZ. Here, we used RIM-BP2
    knock-out (KO) mice and their wild-type (WT) littermates of either sex to investigate
    the role of RIM-BP2 at the endbulb of Held synapse of auditory nerve fibers (ANFs)
    with bushy cells (BCs) of the cochlear nucleus, a fast relay of the auditory pathway
    with high release probability. Disruption of RIM-BP2 lowered release probability
    altering short-term plasticity and reduced evoked EPSCs. Analysis of SV pool dynamics
    during high-frequency train stimulation indicated a reduction of SVs with high
    release probability but an overall normal size of the readily releasable SV pool
    (RRP). The Ca2+-dependent fast component of SV replenishment after RRP depletion
    was slowed. Ultrastructural analysis by superresolution light and electron microscopy
    revealed an impaired topography of presynaptic CaV and a reduction of docked and
    membrane-proximal SVs at the AZ. We conclude that RIM-BP2 organizes the topography
    of CaV, and promotes SV tethering and docking. This way RIM-BP2 is critical for
    establishing a high initial release probability as required to reliably signal
    sound onset information that we found to be degraded in BCs of RIM-BP2-deficient
    mice in vivo. SIGNIFICANCE STATEMENT: Rab-interacting molecule (RIM)-binding proteins
    (BPs) are key organizers of the active zone (AZ). Using a multidisciplinary approach
    to the calyceal endbulb of Held synapse that transmits auditory information at
    rates of up to hundreds of Hertz with submillisecond precision we demonstrate
    a requirement for RIM-BP2 for normal auditory signaling. Endbulb synapses lacking
    RIM-BP2 show a reduced release probability despite normal whole-terminal Ca2+
    influx and abundance of the key priming protein Munc13-1, a reduced rate of SV
    replenishment, as well as an altered topography of voltage-gated (CaV)2.1 Ca2+
    channels, and fewer docked and membrane proximal synaptic vesicles (SVs). This
    hampers transmission of sound onset information likely affecting downstream neural
    computations such as of sound localization.'
acknowledgement: This work was supported by the Deutsche Forschungsgemeinschaft (DFG,
  German Research Foundation) through the Collaborative Sensory Research Center 1286
  [to C.W. (A4) and T.M. (B5)] and under Germany’s Excellence Strategy Grant EXC 2067/1-390729940.
  We thank S. Gerke, A.J. Goldak, and C. Senger-Freitag for expert technical assistance;
  G. Hoch for developing image analysis routines; and S. Chepurwar and N. Strenzke
  for technical support and discussion regarding in vivo experiments. We also thank
  Dr. Christian Rosenmund, Dr. Katharina Grauel, and Dr. Stephan Sigrist for providing
  RIM-BP2 KO mice and Dr. Masahiko Watanabe for providing the anti-neurexin-antibody,
  and Dr. Toshihisa Ohtsuka for the anti-ELKS-antibody. J. Neef for help with the
  STED imaging and image analysis; E. Neher and S. Rizzoli for discussion and comments
  on the manuscript; K. Eguchi for help with the statistical analysis; and C. H. Huang
  and J. Neef for constant support and scientific discussion.
article_processing_charge: No
article_type: original
author:
- first_name: Tanvi
  full_name: Butola, Tanvi
  last_name: Butola
- first_name: Theocharis
  full_name: Alvanos, Theocharis
  last_name: Alvanos
- first_name: Anika
  full_name: Hintze, Anika
  last_name: Hintze
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: David
  full_name: Kleindienst, David
  id: 42E121A4-F248-11E8-B48F-1D18A9856A87
  last_name: Kleindienst
- first_name: Ryuichi
  full_name: Shigemoto, Ryuichi
  id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
  last_name: Shigemoto
  orcid: 0000-0001-8761-9444
- first_name: Carolin
  full_name: Wichmann, Carolin
  last_name: Wichmann
- first_name: Tobias
  full_name: Moser, Tobias
  last_name: Moser
citation:
  ama: Butola T, Alvanos T, Hintze A, et al. RIM-binding protein 2 organizes Ca<sup>21</sup>
    channel topography and regulates release probability and vesicle replenishment
    at a fast central synapse. <i>Journal of Neuroscience</i>. 2021;41(37):7742-7767.
    doi:<a href="https://doi.org/10.1523/JNEUROSCI.0586-21.2021">10.1523/JNEUROSCI.0586-21.2021</a>
  apa: Butola, T., Alvanos, T., Hintze, A., Koppensteiner, P., Kleindienst, D., Shigemoto,
    R., … Moser, T. (2021). RIM-binding protein 2 organizes Ca<sup>21</sup> channel
    topography and regulates release probability and vesicle replenishment at a fast
    central synapse. <i>Journal of Neuroscience</i>. Society for Neuroscience. <a
    href="https://doi.org/10.1523/JNEUROSCI.0586-21.2021">https://doi.org/10.1523/JNEUROSCI.0586-21.2021</a>
  chicago: Butola, Tanvi, Theocharis Alvanos, Anika Hintze, Peter Koppensteiner, David
    Kleindienst, Ryuichi Shigemoto, Carolin Wichmann, and Tobias Moser. “RIM-Binding
    Protein 2 Organizes Ca<sup>21</sup> Channel Topography and Regulates Release Probability
    and Vesicle Replenishment at a Fast Central Synapse.” <i>Journal of Neuroscience</i>.
    Society for Neuroscience, 2021. <a href="https://doi.org/10.1523/JNEUROSCI.0586-21.2021">https://doi.org/10.1523/JNEUROSCI.0586-21.2021</a>.
  ieee: T. Butola <i>et al.</i>, “RIM-binding protein 2 organizes Ca<sup>21</sup>
    channel topography and regulates release probability and vesicle replenishment
    at a fast central synapse,” <i>Journal of Neuroscience</i>, vol. 41, no. 37. Society
    for Neuroscience, pp. 7742–7767, 2021.
  ista: Butola T, Alvanos T, Hintze A, Koppensteiner P, Kleindienst D, Shigemoto R,
    Wichmann C, Moser T. 2021. RIM-binding protein 2 organizes Ca<sup>21</sup> channel
    topography and regulates release probability and vesicle replenishment at a fast
    central synapse. Journal of Neuroscience. 41(37), 7742–7767.
  mla: Butola, Tanvi, et al. “RIM-Binding Protein 2 Organizes Ca<sup>21</sup> Channel
    Topography and Regulates Release Probability and Vesicle Replenishment at a Fast
    Central Synapse.” <i>Journal of Neuroscience</i>, vol. 41, no. 37, Society for
    Neuroscience, 2021, pp. 7742–67, doi:<a href="https://doi.org/10.1523/JNEUROSCI.0586-21.2021">10.1523/JNEUROSCI.0586-21.2021</a>.
  short: T. Butola, T. Alvanos, A. Hintze, P. Koppensteiner, D. Kleindienst, R. Shigemoto,
    C. Wichmann, T. Moser, Journal of Neuroscience 41 (2021) 7742–7767.
date_created: 2021-09-27T14:33:13Z
date_published: 2021-09-15T00:00:00Z
date_updated: 2023-08-14T06:56:30Z
day: '15'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1523/JNEUROSCI.0586-21.2021
external_id:
  isi:
  - '000752287700005'
  pmid:
  - '34353898'
file:
- access_level: open_access
  checksum: 769ab627c7355a50ccfd445e43a5f351
  content_type: application/pdf
  creator: dernst
  date_created: 2022-05-31T09:10:15Z
  date_updated: 2022-05-31T09:10:15Z
  file_id: '11423'
  file_name: 2021_JourNeuroscience_Butola.pdf
  file_size: 11571961
  relation: main_file
  success: 1
file_date_updated: 2022-05-31T09:10:15Z
has_accepted_license: '1'
intvolume: '        41'
isi: 1
issue: '37'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: 7742-7767
pmid: 1
publication: Journal of Neuroscience
publication_identifier:
  eissn:
  - 1529-2401
  issn:
  - 0270-6474
publication_status: published
publisher: Society for Neuroscience
quality_controlled: '1'
scopus_import: '1'
status: public
title: RIM-binding protein 2 organizes Ca<sup>21</sup> channel topography and regulates
  release probability and vesicle replenishment at a fast central synapse
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: 41
year: '2021'
...
---
_id: '7398'
abstract:
- lang: eng
  text: 'Transporters of the solute carrier 6 (SLC6) family translocate their cognate
    substrate together with Na+ and Cl−. Detailed kinetic models exist for the transporters
    of GABA (GAT1/SLC6A1) and the monoamines dopamine (DAT/SLC6A3) and serotonin (SERT/SLC6A4).
    Here, we posited that the transport cycle of individual SLC6 transporters reflects
    the physiological requirements they operate under. We tested this hypothesis by
    analyzing the transport cycle of glycine transporter 1 (GlyT1/SLC6A9) and glycine
    transporter 2 (GlyT2/SLC6A5). GlyT2 is the only SLC6 family member known to translocate
    glycine, Na+, and Cl− in a 1:3:1 stoichiometry. We analyzed partial reactions
    in real time by electrophysiological recordings. Contrary to monoamine transporters,
    both GlyTs were found to have a high transport capacity driven by rapid return
    of the empty transporter after release of Cl− on the intracellular side. Rapid
    cycling of both GlyTs was further supported by highly cooperative binding of cosubstrate
    ions and substrate such that their forward transport mode was maintained even
    under conditions of elevated intracellular Na+ or Cl−. The most important differences
    in the transport cycle of GlyT1 and GlyT2 arose from the kinetics of charge movement
    and the resulting voltage-dependent rate-limiting reactions: the kinetics of GlyT1
    were governed by transition of the substrate-bound transporter from outward- to
    inward-facing conformations, whereas the kinetics of GlyT2 were governed by Na+
    binding (or a related conformational change). Kinetic modeling showed that the
    kinetics of GlyT1 are ideally suited for supplying the extracellular glycine levels
    required for NMDA receptor activation.'
article_processing_charge: No
article_type: original
author:
- first_name: Fatma Asli
  full_name: Erdem, Fatma Asli
  last_name: Erdem
- first_name: Marija
  full_name: Ilic, Marija
  last_name: Ilic
- first_name: Peter
  full_name: Koppensteiner, Peter
  id: 3B8B25A8-F248-11E8-B48F-1D18A9856A87
  last_name: Koppensteiner
  orcid: 0000-0002-3509-1948
- first_name: Jakub
  full_name: Gołacki, Jakub
  last_name: Gołacki
- first_name: Gert
  full_name: Lubec, Gert
  last_name: Lubec
- first_name: Michael
  full_name: Freissmuth, Michael
  last_name: Freissmuth
- first_name: Walter
  full_name: Sandtner, Walter
  last_name: Sandtner
citation:
  ama: Erdem FA, Ilic M, Koppensteiner P, et al. A comparison of the transport kinetics
    of glycine transporter 1 and glycine transporter 2. <i>The Journal of General
    Physiology</i>. 2019;151(8):1035-1050. doi:<a href="https://doi.org/10.1085/jgp.201912318">10.1085/jgp.201912318</a>
  apa: Erdem, F. A., Ilic, M., Koppensteiner, P., Gołacki, J., Lubec, G., Freissmuth,
    M., &#38; Sandtner, W. (2019). A comparison of the transport kinetics of glycine
    transporter 1 and glycine transporter 2. <i>The Journal of General Physiology</i>.
    Rockefeller University Press. <a href="https://doi.org/10.1085/jgp.201912318">https://doi.org/10.1085/jgp.201912318</a>
  chicago: Erdem, Fatma Asli, Marija Ilic, Peter Koppensteiner, Jakub Gołacki, Gert
    Lubec, Michael Freissmuth, and Walter Sandtner. “A Comparison of the Transport
    Kinetics of Glycine Transporter 1 and Glycine Transporter 2.” <i>The Journal of
    General Physiology</i>. Rockefeller University Press, 2019. <a href="https://doi.org/10.1085/jgp.201912318">https://doi.org/10.1085/jgp.201912318</a>.
  ieee: F. A. Erdem <i>et al.</i>, “A comparison of the transport kinetics of glycine
    transporter 1 and glycine transporter 2,” <i>The Journal of General Physiology</i>,
    vol. 151, no. 8. Rockefeller University Press, pp. 1035–1050, 2019.
  ista: Erdem FA, Ilic M, Koppensteiner P, Gołacki J, Lubec G, Freissmuth M, Sandtner
    W. 2019. A comparison of the transport kinetics of glycine transporter 1 and glycine
    transporter 2. The Journal of General Physiology. 151(8), 1035–1050.
  mla: Erdem, Fatma Asli, et al. “A Comparison of the Transport Kinetics of Glycine
    Transporter 1 and Glycine Transporter 2.” <i>The Journal of General Physiology</i>,
    vol. 151, no. 8, Rockefeller University Press, 2019, pp. 1035–50, doi:<a href="https://doi.org/10.1085/jgp.201912318">10.1085/jgp.201912318</a>.
  short: F.A. Erdem, M. Ilic, P. Koppensteiner, J. Gołacki, G. Lubec, M. Freissmuth,
    W. Sandtner, The Journal of General Physiology 151 (2019) 1035–1050.
date_created: 2020-01-29T16:06:29Z
date_published: 2019-07-03T00:00:00Z
date_updated: 2023-09-07T14:52:23Z
day: '03'
ddc:
- '570'
department:
- _id: RySh
doi: 10.1085/jgp.201912318
external_id:
  isi:
  - '000478792500008'
  pmid:
  - '31270129'
file:
- access_level: open_access
  checksum: 5706b4ccd74ee3e50bf7ecb2a203df71
  content_type: application/pdf
  creator: dernst
  date_created: 2020-02-05T07:20:32Z
  date_updated: 2020-07-14T12:47:57Z
  file_id: '7450'
  file_name: 2019_JGP_Erdem.pdf
  file_size: 2641297
  relation: main_file
file_date_updated: 2020-07-14T12:47:57Z
has_accepted_license: '1'
intvolume: '       151'
isi: 1
issue: '8'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-sa/4.0/
month: '07'
oa: 1
oa_version: Published Version
page: 1035-1050
pmid: 1
publication: The Journal of General Physiology
publication_identifier:
  eissn:
  - 1540-7748
  issn:
  - 0022-1295
publication_status: published
publisher: Rockefeller University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: A comparison of the transport kinetics of glycine transporter 1 and glycine
  transporter 2
tmp:
  image: /images/cc_by_nc_sa.png
  legal_code_url: https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode
  name: Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC
    BY-NC-SA 4.0)
  short: CC BY-NC-SA (4.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 151
year: '2019'
...