---
_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
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'
...