Palmitoylation

S-Palmitoylation is the covalent attachment of fatty acids, such as palmitic acid, to cysteine residues of membrane proteins. [ Linder, M.E., "Reversible modification of proteins with thioester-linked fatty acids," "Protein Lipidation", F. Tamanoi and D.S. Sigman, eds., pp. 215-40 (San Diego, CA: Academic Press, 2000).]

The precise function of palmitoylation depends on the particular protein being considered. Palmitoylation enhances the hydrophobicity of proteins and contributes to their membrane association. Palmitoylation also appears to play a significant role in subcellular trafficking of proteins between membrane compartments, as well as in modulating protein-protein interactions. [ Basu, J., "Protein palmitoylation and dynamic modulation of protein function," "Current Science", Vol. 87, No. 2, pp. 212-17 (25 July 2004), http://www.ias.ac.in/currsci/jul252004/contents.htm ] In contrast to prenylation and myristoylation, palmitoylation is reversible. This allows the cell to dynamically regulate the location of specific proteins.

An example of a protein that undergoes palmitoylation is hemagglutinin, a membrane glycoprotein used by influenza to attach to host cell receptors. [ influenza viruses, the encyclopedia of virology, http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B7GG4-4CK7DHD-S&_rdoc=5&_hierId=42642&_refWorkId=141&_explode=42642&_alpha=I&_fmt=full&_orig=na&_docanchor=&_idxType=AR&view=c&_ct=10&_acct=C000011279&_version=1&_urlVersion=0&_userid=5399531&md5=607bbb1a7d18138457365550b9471eb5. ]

Because S-palmitoylation is a dynamic, post-translational process, it is believed to be employed by the cell to alter the subcellular localization, protein-protein interactions, or binding capacities of a protein.

The palmitoylation cycles of a wide array of enzymes have been characterized in the past few years, including H-Ras, Gsα, the β2-adrenergic receptor, and endothelial nitric oxide synthase (eNOS).

Palmitoylation in Synaptic Plasticity

Recently, scientist have appreciated the significance of attaching long hydrophobic chains to specific proteins in cell signaling pathways. A good example of its significance is in the clustering of proteins in the synapse. A major mediator of protein clustering in the synapse is the postsynaptic density (95kD) protein, PSD-95. When this protein is palmitoylated it is restricted to the membrane. This restriction to the membrane allows it to bind to and cluster ion channels in the postsynaptic membrane. Also, in the presynaptic neuron, palmitoylation of SNAP-25 allows the SNARE complex to dissociate during vesicle fusion. This provides a role for palmitoylation in regulating neurotransmitter release. ["Molecular Mechanisms of Synaptogenesis." Edited by Alexander Dityatev and Alaa El-Husseini. Springer: New York, NY. 2006. pg. 72-75]

References

*Smotrys J and Linder A. (2004) [http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biochem.73.011303.073954?cookieSet=1&journalCode=biochem "Palmitoylation of Intracellular Signaling Proteins: Regulation and Function"] . Annu Rev Biochem 73:559-87.
*Resh, M. (2006) [http://stke.sciencemag.org/cgi/content/abstract/2006/359/re14 "Palmitoylation of Ligands, Receptors, and Intracellular Signaling Molecules"] . Sci STK. 359 October 31.
*Linder M and Deschenes R. (2007) Palmitoylation: policing protein stability and traffic. Nature 8: 74-84.