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Vesicular Glutamate Transporters (SLCA17 A6, 7, 8) Control Synaptic Phosphate Levels
Cyril Cheret1, Marcelo Ganzella2, Julia Preobraschenski2
1Institute for Integrative Neuroanatomy, Charité, Medical University of Berlin, 10115 Berlin, Germany.
Cell Reports
|January 13, 2021
Summary
Vesicular glutamate transporters (VGLUTs) have a dual role in neurons, facilitating both glutamate loading into vesicles and inorganic phosphate (Pi) uptake. This study reveals VGLUTs
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Vesicular glutamate transporters (VGLUTs) are crucial for neurotransmission by packaging glutamate into synaptic vesicles.
- The identified sodium-dependent inorganic phosphate (Pi) transport activity of VGLUTs has unclear physiological significance.
- VGLUTs augment intracellular Pi levels upon heterologous expression.
Purpose of the Study:
- To investigate the physiological role of VGLUT-mediated inorganic phosphate (Pi) transport in neurons.
- To elucidate the functional interplay between glutamate and Pi transport by VGLUTs.
- To determine the impact of VGLUTs on neuronal Pi homeostasis.
Main Methods:
- Utilized neuronal models to study VGLUT translocation during exocytosis.
- Examined Pi uptake and efflux mechanisms mediated by VGLUTs.
- Investigated Pi transport in synaptosomes from VGLUT2 knockout mice.
- Employed a nanobody to block VGLUT1 function and assess Pi transport.
Main Results:
- VGLUT translocation to the plasma membrane significantly increases Pi uptake.
- VGLUT-mediated Pi influx is balanced by Pi efflux.
- Synaptosomes lacking VGLUTs exhibit reduced cytosolic Pi and impaired Pi import.
- Glutamate partially competes with Na+/Pi uptake, and blocking VGLUT1 inhibits Pi transport.
Conclusions:
- VGLUTs possess a dual function essential for both vesicular glutamate loading and neuronal Pi restoration.
- VGLUT-mediated Pi transport plays a critical role in maintaining neuronal phosphate homeostasis.
- Understanding VGLUT dual function offers insights into neurotransmitter and phosphate regulation in the brain.
Keywords:
Na(+)-dependent transportPi homeostasisVGLUTsglutamatephosphatesubstrate binding sitesynapseMore Related Videos
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