|
| Status |
Public on Nov 09, 2021 |
| Title |
GluN3A-NMDA receptors constrain protein synthesis and memory by limiting synaptic GIT1/mTORC1 assembly |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Protein synthesis has been implicated in learning and memory, but regulatory mechanisms operating at the synaptic level have not been identified yet. Here we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mTOR kinase and Raptor that couple synaptic stimuli to mTORC1-dependent protein synthesis; and identify non-conventional NMDA receptors containing GluN3A subunits as key negative regulators of GIT1’s binding to mTOR. GluN3A removal enables GIT1/mTOR complex formation, switches on mTORC1-dependent synthesis of plasticity proteins and enhances memory. The memory enhancement becomes evident with light training and can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood. Notably, unlike the memory enhancement seen after global manipulations of translation, GluN3A deletion does not compromise memory flexibility or extinction. These findings identify a novel regulatory mechanism whereby GIT1/GluN3A interactions set local modes of protein synthesis and gate memory formation, offering a potentially selective target for cognitive enhancement.
|
| |
|
| Overall design |
mRNA profiles from DIV14 cortical primary cultured neurons expressing exogenous GFP-GluN3A or GFP in basal conditions or upon a 1h treatment with BDNF 100ng/ml or Bicuculine 50uM.
|
| |
|
| Contributor(s) |
Conde-Dusman MJ, Niñerola S, Barco A, Pérez-Otaño I |
| Citation(s) |
34787081 |
| |
| Submission date |
Jun 01, 2021 |
| Last update date |
Feb 08, 2022 |
| Contact name |
Sergio Niñerola |
| E-mail(s) |
sninerola@umh.es
|
| Phone |
+34646912958
|
| Organization name |
CSIC-Instituto de Neurociencias de Alicante
|
| Department |
Molecular Neurobiology and Neuropathology
|
| Lab |
Transcriptional and epigenetic mechanisms of neuronal plasticity
|
| Street address |
Avenida Santiago Ramon y Cajal, s/n
|
| City |
San Juan de Alicante |
| State/province |
Alicante |
| ZIP/Postal code |
03550 |
| Country |
Spain |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (19)
|
|
| Relations |
| BioProject |
PRJNA734306 |
| SRA |
SRP322154 |
Less...
More...