DGKι regulates presynaptic release during mGluR-dependent LTD

• Published in: The EMBO journal Vol. 30; no. 1; pp. 165 - 180
• Main Authors: Yang, Jinhee, Seo, Jinsoo, Nair, Ramya, Han, Seungnam, Jang, Seil, Kim, Karam, Han, Kihoon, Paik, Sang Kyoo, Choi, Jeonghoon, Lee, Seunghoon, Bae, Yong Chul, Topham, Matthew K, Prescott, Stephen M, Rhee, Jeong-Seop, Choi, Se-Young, Kim, Eunjoon
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 05-01-2011; Nature Publishing Group UK; Nature Publishing Group
• Subjects: Animals; Brain - metabolism; Brain - ultrastructure; Cell Line; Cells, Cultured; diacylglycerol kinase; Diacylglycerol Kinase - analysis; Diacylglycerol Kinase - genetics; Diacylglycerol Kinase - metabolism; Dizocilpine Maleate - metabolism; Gene Deletion; Gene Expression; Humans; long-term depression; metabotropic glutamate receptors; Mice; Nerve Tissue Proteins - metabolism; Neurons - metabolism; Neurons - ultrastructure; Neurotransmitter Agents - metabolism; phospholipase C; Protein Kinase C - metabolism; PSD-95; Rats; Rats, Sprague-Dawley; Receptors, Metabotropic Glutamate - metabolism; Receptors, N-Methyl-D-Aspartate - metabolism; Synapses - metabolism; Synaptic Transmission; phospholipase C; metabotropic glutamate receptors; diacylglycerol kinase; long‐term depression; PSD‐95
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1038/emboj.2010.286

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.
Diacylglycerol (DAG) is a second messenger acting in synaptic signalling. The DAG metabolizing enzyme DGKι regulates presynaptic neurotransmitter release and PSD‐95 family proteins promote its synaptic localization.