Journal
JOURNAL OF NEUROSCIENCE
Volume 33, Issue 39, Pages 15401-15407Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1283-13.2013
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Funding
- NIH
- Howard Hughes Medical Institute
- Shriners Hospitals for Children
- Millipore Corporation
- Grants-in-Aid for Scientific Research [22680029] Funding Source: KAKEN
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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.
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