The mechanism and functional roles of protein palmitoylation in the nervous system

Palmitoylation refers to the covalent attachment of long-chain fatty acids, mostly palmitic acid, to the side chain of cysteine residues of proteins. In recent years, a considerable number of functionally relevant nervous system proteins including ion channels, neurotransmitter receptors, signal transduction components and cell-adhesion molecules have been found to be palmitoylated. However, the lack of a generalized and unambiguous role for the fatty acids in these proteins has questioned the importance of palmitoylation in the functioning of the nervous system. Last year, it was found that the deficiency of palmitoyl-protein thioesterase (PPT), one of the enzymes responsible for the removal of palmitate from proteins, is the underlying cause of infantile neuronal ceroid lipofuscinosis (INCL). This finding not only constitutes a step forward in elucidating the pathogenesis of INCL, but it also provides new impetus in the search for the function(s) of protein palmitoylation. This work succinctly outlines the molecular mechanisms involved in dynamic acylation and the potential biological role(s) of this modification, and it constitutes an introduction to those presentations in this issue which specifically deal with the pathogenic mechanisms of INCL.