Changes in synaptic strength at synapses in the brain are thought to provide the cellular basis for learning and memory. The key excitatory neurotransmitter receptors known as AMPA (short for α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors are anchored in place at synapses through interactions with a scaffolding protein known as postsynaptic density protein-95 (PSD-95). PSD-95 itself is posttraslationally modified by addition of the 16-carbon fatty acid palmitate on its NH2-terminus. El-Husseini and colleagues now report that glutamate receptor activity at the synapse enhances the rate at which cycles of palmitoylation and depalmitoylation of PSD-95 occur in cultured hippocampal neurons. Pharmacological inhibition of palmitoylation caused dispersal of PSD-95 away from the synapse and inhibited AMPA-receptor-mediated signaling at the synapse. The authors conclude that receptor-stimulated turnover of palmitate on PSD-95 provides a mechanism to restrain neurotransmitter signaling and thus represents an important control point for regulation of synaptic function.
A. E.-D. El-Husseini, E. Schnell, S. Dakoji, N. Sweeney, Q. Zhou, O. Prange, C. Gauthier-Campbell, A. Aguilera-Moreno, R. A. Nicoll, D. S. Bredt, Synaptic strength regulated by palmitate cycling on PSD-95. Cell 108, 849-863 (2002). [Online Journal]
