OVERVIEW - PROTEIN PALMITOYLATION IN THE NERVOUS-SYSTEM - CURRENT VIEWS AND UNSOLVED PROBLEMS

Palmitoylation refers to a dynamic post-translational modification of proteins involving the covalent attachment of long-chain fatty acids t o the side chains of cysteine, threonine or serine residues. In recent years, palmitoylation has been identified as a widespread modificatio n bf both viral and cellular proteins. Because of its dynamic nature, protein palmitoylation, like phosphorylation, appears to have a crucia l role in the functioning of the nervous system. Several important que stions regarding the post-translational acylation of cysteine residues in proteins are briefly discussed: (a) What are the molecular mechani sms involved in dynamic acylation? (b) What are the determinants of th e fatty acid specificity and the structural requirements of the accept or proteins? (c) What are the physiological signals regulating this ty pe of protein modification, and (d) What is the biological role(s) of this reaction with respect to the functioning of specific nervous syst em proteins? We also present the current experimental obstacles that h ave to be overcome to fully understand the biology of this dynamic mod ification.