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

Research output: Contribution to journalArticle

409 Citations (Scopus)

Abstract

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
JournalCell
Volume108
Issue number6
DOIs
StatePublished - Mar 22 2002
Externally publishedYes

Fingerprint

AMPA Receptors
Palmitates
Lipoylation
Glutamate Receptors
Plasticity
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Cell membranes
Neurotransmitter Receptor
Neuronal Plasticity
Glutamic Acid
Protein Transport
Synapses
Cluster Analysis
Cell Membrane
Proteins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

El-Husseini, A. E. D., Schnell, E., Dakoji, S., Sweeney, N., Zhou, Q., Prange, O., ... Bredt, D. S. (2002). Synaptic strength regulated by palmitate cycling on PSD-95. Cell, 108(6), 849-863. https://doi.org/10.1016/S0092-8674(02)00683-9

Synaptic strength regulated by palmitate cycling on PSD-95. / El-Husseini, Alaa El Din; Schnell, Eric; Dakoji, Srikanth; Sweeney, Neal; Zhou, Qiang; Prange, Oliver; Gauthier-Campbell, Catherine; Aguilera-Moreno, Andrea; Nicoll, Roger A.; Bredt, David S.

In: Cell, Vol. 108, No. 6, 22.03.2002, p. 849-863.

Research output: Contribution to journalArticle

El-Husseini, AED, Schnell, E, Dakoji, S, Sweeney, N, Zhou, Q, Prange, O, Gauthier-Campbell, C, Aguilera-Moreno, A, Nicoll, RA & Bredt, DS 2002, 'Synaptic strength regulated by palmitate cycling on PSD-95', Cell, vol. 108, no. 6, pp. 849-863. https://doi.org/10.1016/S0092-8674(02)00683-9
El-Husseini AED, Schnell E, Dakoji S, Sweeney N, Zhou Q, Prange O et al. Synaptic strength regulated by palmitate cycling on PSD-95. Cell. 2002 Mar 22;108(6):849-863. https://doi.org/10.1016/S0092-8674(02)00683-9
El-Husseini, Alaa El Din ; Schnell, Eric ; Dakoji, Srikanth ; Sweeney, Neal ; Zhou, Qiang ; Prange, Oliver ; Gauthier-Campbell, Catherine ; Aguilera-Moreno, Andrea ; Nicoll, Roger A. ; Bredt, David S. / Synaptic strength regulated by palmitate cycling on PSD-95. In: Cell. 2002 ; Vol. 108, No. 6. pp. 849-863.
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