The intracellular dynamic of protein palmitoylation

Salaun, Christine; Greaves, Jennifer; Chamberlain, Luke H.

Therefore, it is clear that a major function of palmitoylation is to mediate stable membrane attachment of soluble proteins. However, the effects of this posttranslational modification are more complex and diverse than that of a simple membrane anchor, and indeed, many transmembrane proteins are also palmitoylated. Analyses of different proteins and systems have revealed that palmitoylation has many distinct effects on modified proteins, regulating protein trafficking, protein stability, membrane microlocalization, and protein-protein interactions (Resh, 2006a,b; Greaves and Chamberlain, 2007; Linder and Deschenes, 2007; Greaves et al., 2009b; Noritake et al., 2009) . Although these effects of palmitoylation appear diverse, they are likely determined by two particular properties of palmitate: Figure 1 . Regulation of membrane binding and trafficking of peripheral proteins by palmitoylation. (A) Proteins modified with single lipid groups (prenylation or N-myristoylation; green circles) have a weak membrane affinity that allows transient membrane interaction. Palmitoylation by membrane-bound DHHC proteins promotes stable membrane association by kinetic trapping (Shahinian and Silvius, 1995) . Note that some peripheral proteins are exclusively palmitoylated, and these proteins were suggested to interact with membranes before palmitoylation by way of an intrinsic weak membrane affinity (Greaves et al., , 2009a . (B) Palmitoylation of Ras-farnesyl by Golgi-localized DHHC proteins leads to a dramatic increase in membrane affinity by kinetic trapping. This increased membrane residency facilitates entry of palmitoylated Ras (red circles) into transport vesicles that deliver it to the plasma membrane. It is possible that palmitoylation also serves to move Ras into cholesterol-rich domains from which Golgi exit vesicles are formed . Depalmitoylation of Ras can occur anywhere in the cell, perhaps modulated by Apt1, resulting in membrane release and cytosolic diffusion before repalmitoylation at the Golgi. For simplicity, the figure only depicts depalmitoylation occurring at the plasma membrane. This palmitoylation/depalmitoylation regulation of protein sorting is not specific for Ras proteins and may be a common mechanism underlying the sorting of many peripheral palmitoylated proteins (Kanaani et al., 2008; Tsutsumi et al., 2009; Rocks et al., 2010) .