This title appears in the Scientific Report :
2017
Please use the identifier:
http://hdl.handle.net/2128/16344 in citations.
Please use the identifier: http://dx.doi.org/10.1038/s41467-017-02367-6 in citations.
VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses
VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses
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...
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Personal Name(s): | Martineau, Magalie (Corresponding author) |
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Guzman, Raul / Fahlke, Christoph / Klingauf, Jürgen (Corresponding author) | |
Contributing Institute: |
Zelluläre Biophysik; ICS-4 |
Published in: | Nature Communications, 8 (2017) 1, S. 2279 |
Imprint: |
London
Nature Publishing Group
2017
|
PubMed ID: |
29273736 |
DOI: |
10.1038/s41467-017-02367-6 |
Document Type: |
Journal Article |
Research Program: |
Engineering Cell Function |
Link: |
OpenAccess OpenAccess |
Publikationsportal JuSER |
Please use the identifier: http://dx.doi.org/10.1038/s41467-017-02367-6 in citations.
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. |