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Publication : Vesicular Glutamate Transporters (SLCA17 A6, 7, 8) Control Synaptic Phosphate Levels.

First Author  Cheret C Year  2021
Journal  Cell Rep Volume  34
Issue  2 Pages  108623
PubMed ID  33440152 Mgi Jnum  J:311401
Mgi Id  MGI:6716135 Doi  10.1016/j.celrep.2020.108623
Citation  Cheret C, et al. (2021) Vesicular Glutamate Transporters (SLCA17 A6, 7, 8) Control Synaptic Phosphate Levels. Cell Rep 34(2):108623
abstractText  Vesicular glutamate transporters (VGLUTs) fill synaptic vesicles with glutamate. VGLUTs were originally identified as sodium-dependent transporters of inorganic phosphate (Pi), but the physiological relevance of this activity remains unclear. Heterologous expression of all three VGLUTs greatly augments intracellular Pi levels. Using neuronal models, we show that translocation of VGLUTs to the plasma membrane during exocytosis results in highly increased Pi uptake. VGLUT-mediated Pi influx is counteracted by Pi efflux. Synaptosomes prepared from perinatal VGLUT2(-/-) mice that are virtually free of VGLUTs show drastically reduced cytosolic Pi levels and fail to import Pi. Glutamate partially competes with sodium (Na(+))/Pi (NaPi)-uptake mediated by VGLUTs but does not appear to be transported. A nanobody that blocks glutamate transport by binding to the cytoplasmic domain of VGLUT1 abolishes Pi transport when co-expressed with VGLUT1. We conclude that VGLUTs have a dual function that is essential for both vesicular glutamate loading and Pi restoration in neurons.
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