Journal Article FZJ-2018-00034

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VGLUT1 functions as a glutamate/proton exchanger with chloride channel activity in hippocampal glutamatergic synapses

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2017
Nature Publishing Group London

Nature Communications 8(1), 2279 () [10.1038/s41467-017-02367-6]

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Abstract: 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.

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Contributing Institute(s):
  1. Zelluläre Biophysik (ICS-4)
Research Program(s):
  1. 552 - Engineering Cell Function (POF3-552) (POF3-552)

Appears in the scientific report 2017
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Medline ; Creative Commons Attribution CC BY 4.0 ; DOAJ ; OpenAccess ; BIOSIS Previews ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; IF >= 10 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection ; Zoological Record
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 Record created 2018-01-03, last modified 2021-01-29