TY - JOUR T1 - DHHC8-Dependent PICK1 Palmitoylation is Required for Induction of Cerebellar Long-Term Synaptic Depression JF - The Journal of Neuroscience JO - J. Neurosci. SP - 15401 LP - 15407 DO - 10.1523/JNEUROSCI.1283-13.2013 VL - 33 IS - 39 AU - Gareth M. Thomas AU - Takashi Hayashi AU - Richard L. Huganir AU - David J. Linden Y1 - 2013/09/25 UR - http://www.jneurosci.org/content/33/39/15401.abstract N2 - The palmitoyl acyltransferase (PAT) DHHC8 is implicated in synaptic regulation but few DHHC8 substrates are known. Here we report that DHHC8 binds and palmitoylates the PDZ domain-containing protein PICK1 at a cysteine residue that is essential for long-term synaptic depression (LTD) in cultured mouse cerebellar Purkinje neurons. Cerebellar LTD is palmitoylation-dependent and induction of LTD requires DHHC8. Furthermore, PICK1 is a critical DHHC8 substrate whose palmitoylation is necessary for LTD. These results identify the first DHHC8 substrate required for a specific form of synaptic plasticity and provide new insights into synaptic roles of palmitoylation. ER -