Synaptic strength regulated by palmitate cycling on PSD-95

Alaa El Din El-Husseini, Eric Schnell, Srikanth Dakoji, Neal Sweeney, Qiang Zhou, Oliver Prange, Catherine Gauthier-Campbell, Andrea Aguilera-Moreno, Roger A. Nicoll, David S. Bredt

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423 Scopus citations


Dynamic regulation of AMPA-type glutamate receptors represents a primary mechanism for controlling synaptic strength, though mechanisms for this process are poorly understood. The palmitoylated postsynaptic density protein, PSD-95, regulates synaptic plasticity and associates with the AMPA receptor trafficking protein, stargazin. Here, we identify palmitate cycling on PSD-95 at the synapse and find that palmitate turnover on PSD-95 is regulated by glutamate receptor activity. Acutely blocking palmitoylation disperses synaptic clusters of PSD-95 and causes a selective loss of synaptic AMPA receptors. We also find that rapid glutamate-mediated AMPA receptor internalization requires depalmitoylation of PSD-95. In a nonneuronal model system, clustering of PSD-95, stargazin, and AMPA receptors is also regulated by ongoing palmitoylation of PSD-95 at the plasma membrane. These studies suggest that palmitate cycling on PSD-95 can regulate synaptic strength and regulates aspects of activity-dependent plasticity.

Original languageEnglish (US)
Pages (from-to)849-863
Number of pages15
Issue number6
StatePublished - Mar 22 2002

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    El-Husseini, A. E. D., Schnell, E., Dakoji, S., Sweeney, N., Zhou, Q., Prange, O., Gauthier-Campbell, C., Aguilera-Moreno, A., Nicoll, R. A., & Bredt, D. S. (2002). Synaptic strength regulated by palmitate cycling on PSD-95. Cell, 108(6), 849-863.