DGKl regulates presynaptic release during mGluR-dependent LTD

Jinhee Yang, Jinsoo Seo, Ramya Nair, Seungnam Han, Seil Jang, Karam Kim, Kihoon Han, Sang Kyoo Paik, Jeonghoon Choi, Seunghoon Lee, Yong Chul Bae, Matthew K. Topham, Stephen M. Prescott, Jeong Seop Rhee, Se Young Choi, Eunjoon Kim

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

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 DGKl. In addition, we establish that DGKl acts presynaptically, a function that contrasts with the known postsynaptic function of DGKl, a close relative of DGKl. Deficiency of DGKl in mice does not affect dendritic spines, but leads to a small increase in presynaptic release probability. In addition, DGKl-/- 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 DGKl-/- synapses. These results suggest that DGKl requires PSD-95 family proteins for synaptic localization and regulates presynaptic DAG signalling and neurotransmitter release during mGluR-LTD.

Original languageEnglish
Pages (from-to)165-180
Number of pages16
JournalEMBO Journal
Volume30
Issue number1
DOIs
Publication statusPublished - 2011 Jan 5
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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    Yang, J., Seo, J., Nair, R., Han, S., Jang, S., Kim, K., Han, K., Paik, S. K., Choi, J., Lee, S., Bae, Y. C., Topham, M. K., Prescott, S. M., Rhee, J. S., Choi, S. Y., & Kim, E. (2011). DGKl regulates presynaptic release during mGluR-dependent LTD. EMBO Journal, 30(1), 165-180. https://doi.org/10.1038/emboj.2010.286