Journal
NATURE NEUROSCIENCE
Volume 12, Issue 2, Pages 156-162Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.2248
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Funding
- Japan Society for the Promotion of Science [17680032]
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [17680032] Funding Source: KAKEN
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Uptake of glutamate into synaptic vesicles is mediated by vesicular glutamate transporters (VGLUTs). Although glutamate uptake has been shown to depend critically on Cl-, the precise contribution of this ion to the transport process is unclear. We found that VGLUT1, and not ClC-3 as proposed previously, represents the major Cl- permeation pathway in synaptic vesicles. Using reconstituted VGLUT1, we found that the biphasic dependence of glutamate transport on extravesicular Cl- is a result of the permeation of this anion through VGLUT1 itself. Moreover, we observed that high luminal Cl- concentrations markedly enhanced loading of glutamate by facilitation of membrane potential-driven uptake and discovered a hitherto unrecognized transport mode of VGLUT1. Because a steep Cl- gradient across the synaptic vesicle membrane exists in endocytosed synaptic vesicles, our results imply that the transport velocity and the final glutamate content are highly influenced, if not determined, by the extracellular Cl- concentration.
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