TY - JOUR
T1 - Synaptic strength regulated by palmitate cycling on PSD-95
AU - El-Husseini, Alaa El Din
AU - Schnell, Eric
AU - Dakoji, Srikanth
AU - Sweeney, Neal
AU - Zhou, Qiang
AU - Prange, Oliver
AU - Gauthier-Campbell, Catherine
AU - Aguilera-Moreno, Andrea
AU - Nicoll, Roger A.
AU - Bredt, David S.
PY - 2002/3/22
Y1 - 2002/3/22
N2 - 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.
AB - 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.
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U2 - 10.1016/S0092-8674(02)00683-9
DO - 10.1016/S0092-8674(02)00683-9
M3 - Article
C2 - 11955437
AN - SCOPUS:18344396972
SN - 0092-8674
VL - 108
SP - 849
EP - 863
JO - Cell
JF - Cell
IS - 6
ER -