Saltar al contenido
Merck

GluN2B-Containing NMDA Receptors Regulate AMPA Receptor Traffic through Anchoring of the Synaptic Proteasome.

The Journal of neuroscience : the official journal of the Society for Neuroscience (2015-06-05)
Joana S Ferreira, Jeannette Schmidt, Pedro Rio, Rodolfo Águas, Amanda Rooyakkers, Ka Wan Li, August B Smit, Ann Marie Craig, Ana Luisa Carvalho
RESUMEN

NMDA receptors play a central role in shaping the strength of synaptic connections throughout development and in mediating synaptic plasticity mechanisms that underlie some forms of learning and memory formation in the CNS. In the hippocampus and the neocortex, GluN1 is combined primarily with GluN2A and GluN2B, which are differentially expressed during development and confer distinct molecular and physiological properties to NMDA receptors. The contribution of each subunit to the synaptic traffic of NMDA receptors and therefore to their role during development and in synaptic plasticity is still controversial. We report a critical role for the GluN2B subunit in regulating NMDA receptor synaptic targeting. In the absence of GluN2B, the synaptic levels of AMPA receptors are increased and accompanied by decreased constitutive endocytosis of GluA1-AMPA receptor. We used quantitative proteomic analysis to identify changes in the composition of postsynaptic densities from GluN2B(-/-) mouse primary neuronal cultures and found altered levels of several ubiquitin proteasome system components, in particular decreased levels of proteasome subunits. Enhancing the proteasome activity with a novel proteasome activator restored the synaptic levels of AMPA receptors in GluN2B(-/-) neurons and their endocytosis, revealing that GluN2B-mediated anchoring of the synaptic proteasome is responsible for fine tuning AMPA receptor synaptic levels under basal conditions.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Anticuerpo anti-transportador de glutamato vesicular 1, serum, Chemicon®
Sigma-Aldrich
Anticuerpo anti-receptor 2 de glutamato, extracelular, clon 6C4, clone 6C4, Chemicon®, from mouse
Sigma-Aldrich
Anticuerpo anti-receptor 1 de glutamato, from rabbit, purified by affinity chromatography
Sigma-Aldrich
Anticuerpo anti-NMDAR1 , clon 54.1, clone 54.1, Chemicon®, from mouse
Sigma-Aldrich
Anti-Glutamate Receptor 1 Antibody, phosphoSer 845, Chemicon®, from rabbit
Sigma-Aldrich
Anti-NMDAR2A Antibody, Chemicon®, from rabbit