Clusters of AMPA receptors (red spots) disperse when PSD-95 palmitoylation is blocked (right).

Bredt/Elsevier

Learning is probably driven by use-dependent changes in synaptic strength. Now, Alaa El-Husseini, David Bredt (University of California at San Francisco, San Francisco, CA), and colleagues have identified regulated protein palmitoylation as one means to control the strength of synapse responses.Synaptic activity is controlled by AMPA channels, which respond to the neurotransmitter glutamate by letting in Na+ until the neuron fires. Ca2+ influx through NMDA receptors (also activated by glutamate) alters synaptic responses by influencing the number of AMPA receptors clustered at the synapse.

It now appears that protein palmitoylation is key to this modulation. The localization of AMPA receptors is controlled by the PDZ domain protein PSD-95, which also clusters at synapses and binds to the AMPA-trafficking protein stargazin. The clustering of PSD-95 is known to require its...

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