Somatostatin receptor 5 is palmitoylated by the interacting ZDHHC5 palmitoyltransferase

Many G-protein coupled receptors are palmitoylated in their C-terminal, intracellular regions. So far no enzymes responsible for this modification have been described. We identified an interaction of the membrane proximal helix 8 of somatostatin receptor 5 (SSTR5) with the N-terminal region of the putative palmitoyltransferase ZDHHC5 using the Ras recruitment interaction screening system. ZDHHC5 and SSTR5 are colocalized at the plasma membrane and can be efficiently coimmunoprecipitated from transfected cells. Coexpression of ZDHHC5 in HEK293 cells increased palmitoylation of SSTR5 whereas knock-down of endogenous ZDHHC5 by siRNAs decreased it. Our data identify the first palmitoyltransferase for a G-protein coupled receptor.Structured summary of protein interactionsSSTR5 physically interacts with ZDHHC5 by ras recruitment system (View interaction)SSTR5 and ZDHHC5 colocalize by fluorescence microscopy (View interaction)SSTR5 physically interacts with ZDHHC5 by pull down (View interaction)

► We search for interaction partners of the G-protein coupled receptor SSTR5.
► Using the Ras recruitment system, we identify the palmitoyl transferase ZDHHC5.
► Interaction involves helix 8 of SSTR5, and the N-terminal part of ZDHHC5.
► Knockdown experiments show that ZDHHC5 is required for palmitoylation of SSTR5.