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04:48
A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate
Published on: July 10, 2018
Molecular determinants of NMDA receptor internalization
K W Roche1, S Standley, J McCallum
1Laboratory of Neurochemistry, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Building 36, Room 5B25, Bethesda, Maryland 20892, USA. rochek@nidcd.nih.gov
Nature Neuroscience
|July 31, 2001
Summary
NMDA receptors, crucial for brain function, are not static at synapses. A specific motif on NR2B mediates their internalization, a process regulated by the protein PSD-95, explaining synaptic stability.
Area of Science:
- Neuroscience
- Molecular and Cellular Biology
- Synaptic Plasticity
Background:
- Synaptic AMPA receptors undergo rapid internalization, influencing neuronal communication.
- Conversely, synaptic NMDA receptors have been considered static, with their stability mechanism unclear.
- The role of scaffolding proteins in NMDA receptor synaptic stability is not fully understood.
Purpose of the Study:
- To investigate the dynamic nature of NMDA receptors at synaptic sites.
- To identify molecular mechanisms governing NMDA receptor internalization.
- To determine the role of scaffolding proteins, specifically PSD-95, in regulating NMDA receptor synaptic stability.
Main Methods:
- Utilized heterologous cell systems and primary neuronal cultures.
- Defined an internalization motif (YEKL) on the C-terminus of the NR2B subunit.
- Investigated the effect of PSD-95 interaction and NR2B's PDZ-binding domain on receptor internalization.
Main Results:
- Demonstrated that NMDA receptors are internalized in both heterologous cells and neurons.
- Identified the YEKL motif on NR2B as critical for mediating receptor internalization.
- Showed that the synaptic protein PSD-95 inhibits NR2B internalization, and its disruption enhances internalization in neurons.
Conclusions:
- NMDA receptors are dynamic and capable of internalization, challenging previous assumptions of their static nature.
- The YEKL motif on NR2B is a key determinant of NMDA receptor internalization.
- PSD-95 plays a crucial role in stabilizing NMDA receptors at synapses by inhibiting their internalization, providing a mechanism for observed synaptic stability.
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