Activation of RAGE leads to the release of glutamate from astrocytes and stimulates calcium signal in neurons
Open Access
- 11 February 2021
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 236 (9), 6496-6506
- https://doi.org/10.1002/jcp.30324
Abstract
The receptor for advanced glycation end products (RAGE) is a signal receptor first shown to be activated by advanced glycation end products, but also by a variety of signal molecules, including pathological advanced oxidation protein products and β‐amyloid. However, most of the RAGE activators have multiple intracellular targets, making it difficult to unravel the exact pathway of RAGE activation. Here, we show that the cell‐impermeable RAGE fragment sequence (60–76) of the V‐domain of the receptor is able to activate RAGE present on the plasma membrane of neurons and, preferentially, astrocytes. This leads to the exocytosis of vesicular glutamate transporter vesicles and the release of glutamate from astrocytes, which stimulate NMDA and AMPA/kainate receptors, resulting in calcium signals predominantly in neurons. Thus, we show a specific mechanism of RAGE activation by the RAGE fragment and propose a mechanism by which RAGE activation can contribute to the neuronal‐astrocytic communication in physiology and pathology.Funding Information
- Russian Science Foundation (20‐64‐46027)
- Engineering and Physical Sciences Research Council (EP/R024898/1)
This publication has 34 references indexed in Scilit:
- The role of receptor for advanced glycation end products (RAGE) in neuronal differentiationJournal of Neuroscience Research, 2012
- Prolonged seizure activity impairs mitochondrial bioenergetics and induces cell deathJournal of Cell Science, 2012
- Optogenetic experimentation on astrocytesExperimental Physiology, 2010
- Novel pathway for an old neurotransmitter: Dopamine-induced neuronal calcium signalling via receptor-independent mechanismsCell Calcium, 2010
- Neural-Activity-Dependent Release of S100B from Astrocytes Enhances Kainate-Induced Gamma OscillationsIn VivoJournal of Neuroscience, 2008
- SDF 1-alpha (CXCL12) triggers glutamate exocytosis from astrocytes on a millisecond time scale: Imaging analysis at the single-vesicle level with TIRF microscopyJournal of Neuroimmunology, 2008
- Viral vectors based on bidirectional cell-specific mammalian promoters and transcriptional amplification strategy for use in vitro and in vivoBMC Biotechnology, 2008
- Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamateNature Neuroscience, 2004
- Actions of ionomycin, 4-BrA23187 and a novel electrogenic Ca2+ ionophore on mitochondria in intact cellsCell Calcium, 2003
- Ionophoretic properties of ferutininCell Calcium, 1997