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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Acyltransferases / genetics
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Acyltransferases / metabolism*
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Animals
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Cycle Proteins
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Cells, Cultured
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Cerebellum / cytology
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Cerebellum / metabolism
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Cerebellum / physiology*
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Cysteine / metabolism
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Lipoylation*
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Long-Term Synaptic Depression*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Mice, Knockout
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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PDZ Domains
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Purkinje Cells / metabolism*
Substances
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Carrier Proteins
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Cell Cycle Proteins
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Membrane Proteins
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Nuclear Proteins
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Prkcabp protein, mouse
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Acyltransferases
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ZDHHC8 protein, mouse
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Cysteine