IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-38340-9.html
   My bibliography  Save this article

Vesicular glutamate transporters are H+-anion exchangers that operate at variable stoichiometry

Author

Listed:
  • Bettina Kolen

    (Molekular- und Zellphysiologie (IBI-1), Forschungszentrum Jülich)

  • Bart Borghans

    (Molekular- und Zellphysiologie (IBI-1), Forschungszentrum Jülich)

  • Daniel Kortzak

    (Molekular- und Zellphysiologie (IBI-1), Forschungszentrum Jülich)

  • Victor Lugo

    (Molekular- und Zellphysiologie (IBI-1), Forschungszentrum Jülich)

  • Cora Hannack

    (Molekular- und Zellphysiologie (IBI-1), Forschungszentrum Jülich)

  • Raul E. Guzman

    (Molekular- und Zellphysiologie (IBI-1), Forschungszentrum Jülich)

  • Ghanim Ullah

    (University of South Florida)

  • Christoph Fahlke

    (Molekular- und Zellphysiologie (IBI-1), Forschungszentrum Jülich)

Abstract

Vesicular glutamate transporters accumulate glutamate in synaptic vesicles, where they also function as a major Cl- efflux pathway. Here we combine heterologous expression and cellular electrophysiology with mathematical modeling to understand the mechanisms underlying this dual function of rat VGLUT1. When glutamate is the main cytoplasmic anion, VGLUT1 functions as H+-glutamate exchanger, with a transport rate of around 600 s−1 at −160 mV. Transport of other large anions, including aspartate, is not stoichiometrically coupled to H+ transport, and Cl- permeates VGLUT1 through an aqueous anion channel with unitary transport rates of 1.5 × 105 s−1 at −160 mV. Mathematical modeling reveals that H+ coupling is sufficient for selective glutamate accumulation in model vesicles and that VGLUT Cl- channel function increases the transport efficiency by accelerating glutamate accumulation and reducing ATP-driven H+ transport. In summary, we provide evidence that VGLUT1 functions as H+-glutamate exchanger that is partially or fully uncoupled by other anions.

Suggested Citation

  • Bettina Kolen & Bart Borghans & Daniel Kortzak & Victor Lugo & Cora Hannack & Raul E. Guzman & Ghanim Ullah & Christoph Fahlke, 2023. "Vesicular glutamate transporters are H+-anion exchangers that operate at variable stoichiometry," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38340-9
    DOI: 10.1038/s41467-023-38340-9
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-38340-9
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-38340-9?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Magalie Martineau & Raul E. Guzman & Christoph Fahlke & Jürgen Klingauf, 2017. "VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    2. Dorine M. Starace & Francisco Bezanilla, 2004. "A proton pore in a potassium channel voltage sensor reveals a focused electric field," Nature, Nature, vol. 427(6974), pages 548-553, February.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Jung-Hwan Choi & Lauren Bayer Horowitz & Niels Ringstad, 2021. "Opponent vesicular transporters regulate the strength of glutamatergic neurotransmission in a C. elegans sensory circuit," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    2. Matthew R Skerritt & Donald L Campbell, 2008. "Non-Native R1 Substitution in the S4 Domain Uniquely Alters Kv4.3 Channel Gating," PLOS ONE, Public Library of Science, vol. 3(11), pages 1-7, November.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38340-9. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.