Synaptic strength regulated by palmitate cycling on PSD-95

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Dynamic regulation of AMPA-type glutamate receptors controls synaptic strength.
• The postsynaptic density protein 95 (PSD-95) is involved in synaptic plasticity and receptor trafficking.
• Mechanisms governing AMPA receptor regulation at the synapse are not fully understood.

Purpose of the Study:

• To investigate the role of palmitoylation of PSD-95 in synaptic plasticity.
• To determine how glutamate receptor activity affects PSD-95 palmitoylation.
• To elucidate the function of PSD-95 palmitate cycling in AMPA receptor trafficking and synaptic strength.

Main Methods:

• Identification of palmitate cycling on PSD-95 at the synapse.
• Assessment of PSD-95 palmitoylation regulation by glutamate receptor activity.
• Analysis of the effects of blocking palmitoylation on synaptic PSD-95 clusters and AMPA receptors.
• Investigation of AMPA receptor internalization dynamics.
• Utilizing a nonneuronal model system to study PSD-95, stargazin, and AMPA receptor clustering.

Main Results:

• Palmitate turnover on PSD-95 is regulated by glutamate receptor activity.
• Acute inhibition of palmitoylation disperses synaptic PSD-95 and reduces synaptic AMPA receptors.
• Glutamate-mediated AMPA receptor internalization requires PSD-95 depalmitoylation.
• Palmitoylation of PSD-95 regulates the clustering of PSD-95, stargazin, and AMPA receptors in a nonneuronal system.

Conclusions:

• Palmitate cycling on PSD-95 is a key mechanism for regulating synaptic strength.
• This process is involved in activity-dependent synaptic plasticity, including AMPA receptor trafficking and internalization.
• The findings highlight a novel regulatory pathway for synaptic function.