期刊
JOURNAL OF NEUROSCIENCE
卷 36, 期 48, 页码 12243-12258出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1473-16.2016
关键词
AMPA receptor; endocytic zone; Homer; Parkin; synapse
资金
- Columbia University startup funds (Departments of Pathology and Cell Biology and Neuroscience)
- National Institutes of Health Grant [NS080967]
- Brain Research Foundation seed grant
Mutations in the gene encoding Parkin, an E3 ubiquitin ligase, lead to juvenile-onset Parkinson's disease by inducing the selective death of midbrain dopaminergic neurons. Accumulating evidence indicates that Parkin also has an important role in excitatory glutamatergic neurotransmission, although its precise mechanism of action remains unclear. Here, we investigate Parkin's role at glutamatergic synapses of rat hippocampal neurons. We find that Parkin-deficient neurons exhibit significantly reduced AMPA receptor (AMPAR)-mediated currents and cell-surface expression, and that these phenotypes result from decreased postsynaptic expression of the adaptor protein Homer1, which is necessary for coupling AMPAR endocytic zones with the postsynaptic density. Accordingly, Parkin loss of function leads to the reduced density of postsynaptic endocytic zones and to impaired AMPAR internalization. These findings demonstrate a novel and essential role for Parkin in glutamatergic neurotransmission, as a stabilizer of postsynaptic Homer1 and the Homer1-linked endocytic machinery necessary for maintaining normal cell-surface AMPAR levels.
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