Multiple palmitoylation of synaptotagmin and the t‐SNARE SNAP‐25

Abstract
Synaptotagmin, a likely calcium sensor for synaptic transmission, and SNAP‐25, a t‐SNARE of the presynaptic plasma membrane, are key proteins for the docking and fusion of synaptic and other vesicles. We report that both synaptotagmin and SNAP‐25 are palmitoylated with their fatty acids attached in a labile thioester‐type bond. A SNAP‐25 mutant with deleted palmitoylation sites is found exclusively in the cytosol after cell fractionation, whereas the palmitoylated form of SNAP‐25 is membrane‐bound, establishing that SNAP‐25 is membrane‐anchored via covalently linked palmitate.