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

doi:10.1016/s0092-8674(02)00683-9

Synaptic strength regulated by palmitate cycling on PSD-95

Cell. 2002 Mar 22;108(6):849-63. doi: 10.1016/s0092-8674(02)00683-9.

Authors

Alaa El-Din El-Husseini¹, Eric Schnell, Srikanth Dakoji, Neal Sweeney, Qiang Zhou, Oliver Prange, Catherine Gauthier-Campbell, Andrea Aguilera-Moreno, Roger A Nicoll, David S Bredt

Affiliation

¹ Department of Physiology, University of California, San Francisco, CA 94143, USA.

PMID: 11955437
DOI: 10.1016/s0092-8674(02)00683-9

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Calcium Channels / genetics
Calcium Channels / metabolism
Cell Membrane / metabolism
Cells, Cultured
Cerebral Cortex / cytology
Disks Large Homolog 4 Protein
Green Fluorescent Proteins
Hippocampus / cytology
Hypoglycemic Agents / pharmacology
Indicators and Reagents / metabolism
Intracellular Signaling Peptides and Proteins
Luminescent Proteins / genetics
Membrane Proteins
Nerve Tissue Proteins / genetics
Nerve Tissue Proteins / metabolism*
Neuronal Plasticity / physiology
Neurons / cytology
Neurons / physiology
Palmitates / metabolism*
Palmitates / pharmacology
Patch-Clamp Techniques
Rats
Receptors, AMPA / genetics
Receptors, AMPA / metabolism
Synapses / metabolism*
Synaptic Transmission / drug effects
Synaptic Transmission / physiology

Substances

Cacng2 protein, rat
Calcium Channels
Disks Large Homolog 4 Protein
Dlg4 protein, rat
Hypoglycemic Agents
Indicators and Reagents
Intracellular Signaling Peptides and Proteins
Luminescent Proteins
Membrane Proteins
Nerve Tissue Proteins
Palmitates
Receptors, AMPA
postsynaptic density proteins
Green Fluorescent Proteins
2-bromopalmitate