S-palmitoylation of synaptic proteins in rat synaptoneurosomes

Temporal and target-specific S-palmitoylation of synaptic proteins supports synapse and neural network plasticity: Synaptic plasticity is a phenomenon essential for learning and memory, which relies on activity-dependent changes in neural connectivity. S-palmitoylation, a reversible posttranslational lipid modification, regulates synaptic protein function by altering protein conformation, localization, trafficking, and their interactions. Despite its known significance in neuronal function, the temporal and protein-specific dynamics of S-palmitoylation during synaptic plasticity remain poorly understood. Proteomic analysis of synaptoneurosomes revealed a palmitoylome including over 700 proteins, with LTP-induced predominant depalmitoylation. Differentially palmitoylated proteins were associated with synaptic vesicle cycling, cytoskeletal dynamics, and neurotransmitter release. Synaptoneurosomes contained active palmitoylation machinery, supporting rapid, target-specific responses to NMDA receptor activation.