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

2021 | journal article; research paper. A publication with affiliation to the University of Göttingen.

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​Vesicular Glutamate Transporters (SLCA17 A6, 7, 8) Control Synaptic Phosphate Levels​
Cheret, C.; Ganzella, M.; Preobraschenski, J. ; Jahn, R.   & Ahnert-Hilger, G.​ (2021) 
Cell Reports34(2) pp. 108623​.​ DOI: https://doi.org/10.1016/j.celrep.2020.108623 

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Authors
Cheret, Cyril; Ganzella, Marcelo; Preobraschenski, Julia ; Jahn, Reinhard ; Ahnert-Hilger, Gudrun
Abstract
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.
Issue Date
2021
Journal
Cell Reports 
Project
EXC 2067: Multiscale Bioimaging 
Working Group
RG Preobraschenski (Biochemistry of Membrane Dynamics) 
External URL
https://mbexc.uni-goettingen.de/literature/publications/232
ISSN
2211-1247
Language
English

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