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

Gareth M. Thomas, Takashi Hayashi, Richard L. Huganir, David J. Linden

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)15401-15407
Number of pages7
JournalJournal of Neuroscience
Volume33
Issue number39
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'DHHC8-dependent PICK1 palmitoylation is required for induction of cerebellar long-term synaptic depression'. Together they form a unique fingerprint.

Cite this