Synaptic removal of diacylglycerol by DGKζ and PSD-95 regulates dendritic spine maintenance

Karam Kim, Jinhee Yang, Xiao Ping Zhong, Myoung Hwan Kim, Yun Sook Kim, Hyun Woo Lee, Seungnam Han, Jeonghoon Choi, Kihoon Han, Jinsoo Seo, Stephen M. Prescott, Matthew K. Topham, Yong Chul Bae, Gary Koretzky, Se Young Choi, Eunjoon Kim

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46 Citations (Scopus)

Abstract

Diacylglycerol (DAG) is an important lipid signalling molecule that exerts an effect on various effector proteins including protein kinase C. A main mechanism for DAG removal is to convert it to phosphatidic acid (PA) by DAG kinases (DGKs). However, it is not well understood how DGKs are targeted to specific subcellular sites and tightly regulates DAG levels. The neuronal synapse is a prominent site of DAG production. Here, we show that DGK is targeted to excitatory synapses through its direct interaction with the postsynaptic PDZ scaffold PSD-95. Overexpression of DGK in cultured neurons increases the number of dendritic spines, which receive the majority of excitatory synaptic inputs, in a manner requiring its catalytic activity and PSD-95 binding. Conversely, DGK knockdown reduces spine density. Mice deficient in DGK expression show reduced spine density and excitatory synaptic transmission. Time-lapse imaging indicates that DGK is required for spine maintenance but not formation. We propose that PSD-95 targets DGK to synaptic DAG-producing receptors to tightly couple synaptic DAG production to its conversion to PA for the maintenance of spine density.

Original languageEnglish
Pages (from-to)1170-1179
Number of pages10
JournalEMBO Journal
Volume28
Issue number8
DOIs
Publication statusPublished - 2009 Apr 22

Keywords

  • DGKζ
  • Diacylglycerol kinase
  • PSD-95
  • phosphatidic acid
  • spine

ASJC Scopus subject areas

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

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  • Cite this

    Kim, K., Yang, J., Zhong, X. P., Kim, M. H., Kim, Y. S., Lee, H. W., Han, S., Choi, J., Han, K., Seo, J., Prescott, S. M., Topham, M. K., Bae, Y. C., Koretzky, G., Choi, S. Y., & Kim, E. (2009). Synaptic removal of diacylglycerol by DGKζ and PSD-95 regulates dendritic spine maintenance. EMBO Journal, 28(8), 1170-1179. https://doi.org/10.1038/emboj.2009.44