Scribble1/AP2 Complex Coordinates NMDA Receptor Endocytic Recycling
2014
Piguel, Nicolas, H | Fievre, Sabine | Blanc, Jean-Michel | Carta, Mario | Moreau, Maïté, M | Moutin, Enora | Pinheiro, Vera, L | Medina, Chantal | Ezan, Jerome | Lasvaux, Léa | Loll, François | Durand, Christelle, M | Chang, Kai | Petralia, Ronald, S | Wenthold, Robert, J | Stephenson, F, Anne | Vuillard, Laurent | Darbon, Hervé | Perroy, Julie | Mulle, Christophe | Montcouquiol, Mireille | Racca, Claudia | Sans, Nathalie | Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale (U1215 Inserm - UB) ; Université de Bordeaux (UB)-Institut François Magendie-Institut National de la Santé et de la Recherche Médicale (INSERM) | Interdisciplinary Institute for Neuroscience / Institut interdisciplinaire de neurosciences [Bordeaux] (IINS) ; Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS) | Institut de Génomique Fonctionnelle (IGF) ; Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) | National Institute on Deafness and other Communication Disorders (NIDCD) ; National Institutes of Health [Bethesda, MD, USA] (NIH) | University College of London [London] (UCL) | Architecture et fonction des macromolécules biologiques (AFMB) ; Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS) | Newcastle University [Newcastle]
International audience
显示更多 [+] 显示较少 [-]英语. The appropriate trafficking of glutamate receptors to synapses is crucial for basic synaptic function and synaptic plasticity. It is now accepted that NMDA receptors (NMDARs) internalize and are recycled at the plasma membrane but also exchange between synaptic and extrasynaptic pools; these NMDAR properties are also key to governing synaptic plasticity. Scribble1 is a large PDZ protein required for synaptogenesis and synaptic plasticity. Herein, we show that the level of Scribble1 is regulated in an activity-dependent manner and that Scribble1 controls the number of NMDARs at the plasma membrane. Notably, Scribble1 prevents GluN2A subunits from undergoing lysosomal trafficking and degradation by increasing their recycling to the plasma membrane following NMDAR activation. Finally, we show that a specific YxxR motif on Scribble1 controls these mechanisms through a direct interaction with AP2. Altogether, our findings define a molecular mechanism to control the levels of synaptic NMDARs via Scribble1 complex signaling.
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