S-Palmitoylation of Synaptic Proteins in Neuronal Plasticity in Normal and Pathological Brains

Protein lipidation is a common post-translational modification of proteins that plays an important role in human physiology and pathology. One form of protein lipidation, S-palmitoylation, involves the addition of a 16-carbon fatty acid (palmitate) onto proteins. This reversible modification may affect the regulation of protein trafficking and stability in membranes. From multiple recent experimental studies, a picture emerges whereby protein S-palmitoylation is a ubiquitous yet discrete molecular switch enabling the expansion of protein functions and subcellular localization in minutes to hours. Neural tissue is particularly rich in proteins that are regulated by S-palmitoylation. A surge of novel methods of detection of protein lipidation at high resolution allowed us to get better insights into the roles of protein palmitoylation in brain physiology and pathophysiology. In this review, we specifically discuss experimental work devoted to understanding the impact of protein palmitoylation on functional changes in the excitatory and inhibitory synapses associated with neuronal activity and neuronal plasticity. The accumulated evidence also implies a crucial role of S-palmitoylation in learning and memory, and brain disorders associated with impaired cognitive functions.

Automated summary

Protein lipidation, specifically S-palmitoylation, is a common post-translational modification that regulates protein trafficking in membranes and has essential roles in human physiology and brain function. Recent experimental studies have shed light on the discrete molecular switch function of protein S-palmitoylation within minutes to hours, expanding protein functions and subcellular localization. This review focuses on the impact of protein palmitoylation on functional changes in synapses associated with neuronal activity and plasticity, highlighting its crucial role in learning, memory, and cognitive functions.