PIGUEL, Nicolas H.; FIEVRE, Sabine; BLANC, Jean-Michel; CARTA, Mario; MOREAU, Maite M.; MOUTIN, Enora; PINHEIRO, Vera L.; MEDINA, Chantal; EZAN, Jerome; LASVAUX, Lea; LOLL, Francois; DURAND, Christelle M.; CHANG, Kai; PETRALIA, Ronald S.; WENTHOLD, Robert J.; STEPHENSON, F. Anne; VUILLARD, Laurent; DARBON, Herve; PERROY, Julie; MULLE, Christophe; MONTCOUQUIOL, Mireille; RACCA, Claudia; SANS, Nathalie

doi:10.1016/j.celrep.2014.09.017

PIGUEL, Nicolas H.
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

FIEVRE, Sabine
Interdisciplinary Institute for Neuroscience / Institut interdisciplinaire de neurosciences [Bordeaux] [IINS]

BLANC, Jean-Michel
Neurocentre Magendie : Physiopathologie de la Plasticité Neuronale [U1215 Inserm - UB]

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Cell Reports. 2014-10-23, vol. 9, n° 2, p. 712-727

Résumé en anglais

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.< Réduire

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https://oskar-bordeaux.fr/handle/20.500.12278/140453

DOI

http://dx.doi.org/10.1016/j.celrep.2014.09.017

Project ANR

Bordeaux Region Aquitaine Initiative for Neuroscience
Caractérisations moléculaire et fonctionnelle de la protéine Scribble 1 au cours du développement du système nerveux central
Signalisation de la polarité cellulaire planaire dans la plasticité synaptique morphofonctionnelle des circuits hippocampiques

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Neurocentre Magendie - U1215

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Scribble1/AP2 Complex Coordinates NMDA Receptor Endocytic Recycling

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DOI

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