Huntingtin-Interacting Protein HIP14 Is a Palmitoyl Transferase Involved in Palmitoylation and Trafficking of Multiple Neuronal Proteins

摘要: In neurons, posttranslational modification by palmitate regulates the trafficking and function of signaling molecules, neurotransmitter receptors, associated synaptic scaffolding proteins. However, enzymatic machinery involved in protein palmitoylation has remained elusive. Here, using biochemical assays, we show that huntingtin (htt) interacting protein, HIP14, is a neuronal palmitoyl transferase (PAT). HIP14 shows remarkable substrate specificity for proteins, including SNAP-25, PSD-95, GAD65, synaptotagmin I, htt. Conversely, catalytically invariant toward paralemmin VII. Exogenous enhances palmitoylation-dependent vesicular several acylated proteins both heterologous cells neurons. Moreover, interference with endogenous expression reduces clustering PSD-95 GAD65 These findings define as mammalian multiple