APP fragment controls both ionotropic and non-ionotropic signaling of NMDA receptors
Helene Marie, Jade Dunot, Sebastien Moreno, Carine Gandin, Paula Pousinha, Mascia Amici, Julien Dupuis, Magalie Uriot, Margarita Anisimova, Samuel Petshow, Alex Winschel, Maria Mensch, Ingrid Bethus, Camilla Giudici, Heike Hampel, Benedikt Wefers, Wolfgang Wurst, Michael Ashby, Bodo Laube, Karen Zito, Jack Mellor, Laurent Groc, Michael Willem · FENS Forum 2024
NMDA receptors (NMDARs) are ionotropic receptors crucial for brain information processing. Yet, evidence also supports an ion flux-independent signaling mode mediating synaptic long-term depression (LTD) and spine shrinkage. How these different modes of NMDAR activity are controlled remains unknown. Here, we identify AETA (Aη), an amyloid-β precursor protein (APP) cleavage product, as an NMDAR modulator with the unique dual regulatory capacity to impact both signaling modes. AETA inhibits ionotropic NMDAR activity, principally of GluN2A containing heteromers, by competing with the co-agonist a
ePoster · Neuroscience