DHHC8-dependent PICK1 palmitoylation is required for induction of cerebellar long-term synaptic depression.

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.

Citation

Gareth M Thomas, Takashi Hayashi, Richard L Huganir, David J Linden. DHHC8-dependent PICK1 palmitoylation is required for induction of cerebellar long-term synaptic depression. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2013 Sep 25;33(39):15401-7

Mesh Tags

Substances

PMID: 24068808

search → result