The intracellular dynamic of protein palmitoylation

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

Many other palmitoylated peripheral proteins do not display obvious steady-state localization at the Golgi but instead associate with the plasma membrane and endosomal membranes (Adamson et al., 1992; Kasahara et al., 2007; Sandilands et al., 2007) . The absence of such proteins from the Golgi might indicate that they are not modified by Golgi-localized DHHC Figure 2 . Regulation of protein localization by palmitoylation dynamics. The illustration depicts three palmitoylated proteins that have different rates of depalmitoylation. In this context, the term depalmitoylation refers to the complete absence of palmitoyl groups on the protein. Rapid depalmitoylation is associated with an enriched steady-state localization on Golgi membranes. This is achieved by depalmitoylation promoting membrane release and subsequent palmitoylation by Golgi-specific DHHC proteins leading to an accumulation at this compartment. Rapid depalmitoylation prevents excessive accumulation on endosomes via vesicular trafficking from the plasma membrane. In contrast, proteins that have a slower rate of depalmitoylation are maintained on membranes for longer and reach endosomal membranes via the plasma membrane. Note that a slower depalmitoylation rate may be achieved by a relative resistance to thioesterases, and/or the presence of many palmitoylated cysteines, and/or palmitoylation by DHHC proteins beyond the Golgi. All of these situations would limit the amount of the protein in a completely depalmitoylated state. This slower rate of depalmitoylation and membrane release limits the steady-state distribution on Golgi membranes.