DGKι regulates presynaptic release during mGluR-dependent LTD
| Autor: | Ramya Nair, Jeong-Seop Rhee, Sang Kyoo Paik, Seungnam Han, Jinsoo Seo, Karam Kim, Seunghoon Lee, Seil Jang, Jinhee Yang, Se-Young Choi, Jeonghoon Choi, Stephen M. Prescott, Eunjoon Kim, Yong Chul Bae, Kihoon Han, Matthew K. Topham |
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| Rok vydání: | 2010 |
| Předmět: |
General Immunology and Microbiology
General Neuroscience Neurotransmission Biology General Biochemistry Genetics and Molecular Biology Cell biology chemistry.chemical_compound Biochemistry chemistry Metabotropic glutamate receptor Postsynaptic potential lipids (amino acids peptides and proteins) Long-term depression Neurotransmitter Molecular Biology Postsynaptic density Protein kinase C Diacylglycerol kinase |
| Zdroj: | The EMBO Journal. 30:165-180 |
| ISSN: | 0261-4189 |
| DOI: | 10.1038/emboj.2010.286 |
| Popis: | Diacylglycerol (DAG) is an important lipid second messenger. DAG signalling is terminated by conversion of DAG to phosphatidic acid (PA) by diacylglycerol kinases (DGKs). The neuronal synapse is a major site of DAG production and action; however, how DGKs are targeted to subcellular sites of DAG generation is largely unknown. We report here that postsynaptic density (PSD)-95 family proteins interact with and promote synaptic localization of DGKι. In addition, we establish that DGKι acts presynaptically, a function that contrasts with the known postsynaptic function of DGKζ, a close relative of DGKι. Deficiency of DGKι in mice does not affect dendritic spines, but leads to a small increase in presynaptic release probability. In addition, DGKι−/− synapses show a reduction in metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) at neonatal (∼2 weeks) stages that involve suppression of a decrease in presynaptic release probability. Inhibition of protein kinase C normalizes presynaptic release probability and mGluR-LTD at DGKι−/− synapses. These results suggest that DGKι requires PSD-95 family proteins for synaptic localization and regulates presynaptic DAG signalling and neurotransmitter release during mGluR-LTD. |
| Databáze: | OpenAIRE |
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