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Updated: Aug 11, 2026

Preparation of Synaptic Plasma Membrane and Postsynaptic Density Proteins Using a Discontinuous Sucrose Gradient
Published on: September 3, 2014
PSD-95 involvement in maturation of excitatory synapses
A E El-Husseini1, E Schnell, D M Chetkovich
1Department of Physiology, University of California, San Francisco 94143, USA.
Overexpression of postsynaptic density-95 (PSD-95) protein drives maturation of glutamatergic synapses in hippocampal neurons. This protein orchestrates synaptic development, enhancing receptor activity, presynaptic terminals, and dendritic spine growth.
Area of Science:
- Neuroscience
- Molecular Biology
- Synaptic Plasticity
Background:
- Postsynaptic density-95 (PSD-95) is a key scaffolding protein in neuronal synapses.
- Its precise role in synaptic development and function remains incompletely understood.
Purpose of the Study:
- To investigate the function of PSD-95 in the maturation of glutamatergic synapses.
- To determine the molecular mechanisms underlying PSD-95's role in synaptic development.
Main Methods:
- Overexpression of PSD-95 in cultured hippocampal neurons.
- Analysis of postsynaptic glutamate receptor clustering and activity.
- Assessment of presynaptic terminal maturation.
- Evaluation of dendritic spine morphology and number.
Main Results:
- PSD-95 overexpression promoted the maturation of glutamatergic synapses.
- Enhanced postsynaptic clustering and activity of glutamate receptors were observed.
- Presynaptic terminal maturation and increased dendritic spine number and size were also induced.
- These effects were dependent on PSD-95 synaptic clustering but not its guanylate kinase domain.
Conclusions:
- PSD-95 plays a crucial role in orchestrating synaptic development.
- The findings suggest PSD-95 is involved in synapse stabilization and plasticity.
- PSD-95 acts as a master regulator of synaptic architecture and function.
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