Palmitoylation and Synaptic Strength

Science's STKE  26 Mar 2002:
Vol. 2002, Issue 125, pp. tw116
DOI: 10.1126/stke.2002.125.tw116

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]