Premium
Activation of RAGE leads to the release of glutamate from astrocytes and stimulates calcium signal in neurons
Author(s) -
Kamynina Anna,
Esteras Noemi,
Koroev Dmitry O.,
Angelova Plamena R.,
Volpina Olga M.,
Abramov Andrey Y.
Publication year - 2021
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.30324
Subject(s) - rage (emotion) , kainate receptor , ampa receptor , glutamate receptor , microbiology and biotechnology , nmda receptor , receptor , astrocyte , glycation , chemistry , exocytosis , biology , neuroscience , biochemistry , central nervous system , membrane
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.