The intracellular dynamic of protein palmitoylation

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

Interplay between palmitoylation and phosphorylation was recognized many years ago for the  2 -adrenergic G proteincoupled receptor (Moffet et al., 1993) . Mutation of the palmitoylated cysteine in the C-terminal tail of this receptor led to an increased level of basal phosphorylation and a loss of coupling to Gs (O'Dowd et al., 1989; Moffet et al., 1993) . The effects of mutating the palmitoylation site were not caused by a loss of palmitoylation per se but rather by the increased phosphorylation of the palmitoylation-deficient mutant (Moffett et al., 1996) . Palmitoylation-phosphorylation interplay has also been reported to regulate trafficking of AMPA and NMDA receptor subunits Lin et al., 2009) . For GluR1 subunits of AMPA receptors, depalmitoylation was suggested to enable the more-efficient phosphorylation of neighboring serine residues. This phosphorylation in turn increased the interaction of GluR1 with 4.1N protein, which modulated plasma membrane internalization and insertion dynamics of AMPA receptors (Lin et al., 2009) . How does palmitoylation regulate phosphorylation? One potential mechanism is membrane insertion of palmitoylated cysteines restricting access of protein kinases to the adjacent phosphorylation sites (Fig. 3 A) .