2. Academic Validation
  3. Vesicular Glutamate Transporters (SLCA17 A6, 7, 8) Control Synaptic Phosphate Levels

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

  • Cell Rep. 2021 Jan 12;34(2):108623. doi: 10.1016/j.celrep.2020.108623.
Cyril Cheret 1,  Marcelo Ganzella 2,  Julia Preobraschenski 2,  Reinhard Jahn 3,  Gudrun Ahnert-Hilger 4
Affiliations

Affiliations

  • 1 Institute for Integrative Neuroanatomy, Charité, Medical University of Berlin, 10115 Berlin, Germany.
  • 2 Laboratory of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, and University of Göttingen, 37077 Göttingen, Germany.
  • 3 Laboratory of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, and University of Göttingen, 37077 Göttingen, Germany. Electronic address: [email protected].
  • 4 Institute for Integrative Neuroanatomy, Charité, Medical University of Berlin, 10115 Berlin, Germany; Laboratory of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, and University of Göttingen, 37077 Göttingen, Germany. Electronic address: [email protected].
PMID: 33440152 DOI: 10.1016/j.celrep.2020.108623
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.

Keywords

Na(+)-dependent transport; Pi homeostasis; VGLUTs; glutamate; phosphate; substrate binding site; synapse.

Figures