The intracellular dynamic of protein palmitoylation

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

In hippocampal neurons, DHHC2 is associated with mobile dendritic vesicles of unknown origin, and total internal reflection microscopy suggested that inhibition of synaptic activity promotes an increase in DHHC2 levels either at or just beneath the plasma membrane . Interestingly, this movement of DHHC2 correlates with enhanced palmitoylation and synaptic clustering of PSD95 (El-Husseini et al., 2002; Noritake et al., 2009) , and depletion of DHHC2 was reported to inhibit the increase in synaptic clustering of PSD95 after synaptic blockade. This work illustrates that dynamic palmitoylation can be achieved without peripheral proteins (such as PSD95) visiting the Golgi. It is interesting to note that depletion of DHHC3, which is localized to the somatic Golgi, also inhibited synaptic accumulation of PSD95. However, in contrast with DHHC2 depletion, knockdown of DHHC3 had no effect on the activity-dependent increase in synaptic clustering of PSD95 . This suggests that Golgi-localized DHHC3 is involved in the initial palmitoylation of newly synthesized PSD95, before dendritic targeting.