RGD Reference Report - Scribble1/AP2 complex coordinates NMDA receptor endocytic recycling. - Rat Genome Database

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Scribble1/AP2 complex coordinates NMDA receptor endocytic recycling.

Authors: 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 
Citation: Piguel NH, etal., Cell Rep. 2014 Oct 23;9(2):712-27. doi: 10.1016/j.celrep.2014.09.017. Epub 2014 Oct 9.
RGD ID: 12050130
Pubmed: (View Article at PubMed) PMID:25310985
DOI: Full-text: DOI:10.1016/j.celrep.2014.09.017

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.

Gene Ontology Annotations    

Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Scrib  (scribble planar cell polarity protein)

Additional Information