VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses
Nat Commun. 2017-12-01; 8(1):
DOI: 10.1038/s41467-017-02367-6
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1. Nat Commun. 2017 Dec 22;8(1):2279. doi: 10.1038/s41467-017-02367-6.
VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity
in hippocampal glutamatergic synapses.
Martineau M(1)(2), Guzman RE(3), Fahlke C(3), Klingauf J(4)(5).
Author information:
(1)Department of Cellular Biophysics, Institute for Medical Physics and
Biophysics, University of Muenster, 48149, Muenster, Germany.
.
(2)University of Bordeaux and Centre National de la Recherche Scientifique,
Interdisciplinary Institute for Neuroscience, UMR 5297, F-33000, Bordeaux,
France. .
(3)Institute of Complex Systems, Zelluläre Biophysik (ICS-4), Forschungszentrum
Jülich, 52425, Jülich, Germany.
(4)Department of Cellular Biophysics, Institute for Medical Physics and
Biophysics, University of Muenster, 48149, Muenster, Germany.
.
(5)IZKF Münster and Cluster of Excellence EXC 1003, Cells in Motion (CiM), 48149,
Muenster, Germany. .
Glutamate is the major excitatory transmitter in the vertebrate nervous system.
To maintain synaptic efficacy, recycling synaptic vesicles (SV) are refilled with
glutamate by vesicular glutamate transporters (VGLUTs). The dynamics and
mechanism of glutamate uptake in intact neurons are still largely unknown. Here,
we show by live-cell imaging with pH- and chloride-sensitive fluorescent probes
in cultured hippocampal neurons of wild-type and VGLUT1-deficient mice that in
SVs VGLUT functions as a glutamate/proton exchanger associated with a
channel-like chloride conductance. After endocytosis most internalized Cl- is
substituted by glutamate in an electrically, and presumably osmotically, neutral
manner, and this process is driven by both the Cl- gradient itself and the proton
motive force provided by the vacuolar H+-ATPase. Our results shed light on the
transport mechanism of VGLUT under physiological conditions and provide a
framework for how modulation of glutamate transport via Cl- and pH can change
synaptic strength.
DOI: 10.1038/s41467-017-02367-6
PMCID: PMC5741633
PMID: 29273736