|
NMDA receptors regulate AMPA receptor traffic through anchoring of the synaptic proteasome| old_uid | 14758 |
|---|
| title | NMDA receptors regulate AMPA receptor traffic through anchoring of the synaptic proteasome |
|---|
| start_date | 2014/12/04 |
|---|
| schedule | 11h |
|---|
| online | no |
|---|
| details | Séminaire Impromptu. Une invitation de Nathalie Sans du Neurocentre. |
|---|
| summary | N-methyl-D-aspartate (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 central nervous system. 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 found a critical role for the GluN2B subunit in regulating NMDA receptor synaptic targeting. In the absence of GluN2B, the synaptic level of AMPA receptors is increased, and accompanied by decreased constitutive endocytosis of GluA1-AMPA receptor and altered levels of several Ubiquitin Proteasome System (UPS) components, in particular decreased levels of proteasome subunits. Enhancing the proteasome activity with a novel proteasome activator rescued the synaptic levels of AMPA receptors in GluN2B(-/-) neurons, revealing that GluN2B-mediated anchoring of the synaptic proteasome is responsible for fine tuning AMPA receptor synaptic levels under basal conditions. |
|---|
| responsibles | Deris |
|---|
| |
|