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

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Authors
Kim, Karam; Yang, Jinhee; Zhong, Xiao-Ping; Kim, Myoung-Hwan; Kim, Yun Sook; Lee, Hyun Woo; Han, Seungnam; Choi, Jeonghoon; Han, Kihoon; Seo, Jinsoo; Prescott, Stephen M; Topham, Matthew K; Bae, Yong Chul; Koretzky, Gary; Choi, Se-Young; Kim, Eunjoon
Issue Date
2009-02
Publisher
Nature Publishing Group
Citation
The EMBO Journal 28:1170-1179
Keywords
DGKζdiacylglycerol kinasephosphatidic acidPSD-95spine
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 DGKζ is targeted to excitatory synapses through its direct interaction with the postsynaptic PDZ scaffold PSD-95. Overexpression of DGKζ 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, DGKζ knockdown reduces spine density. Mice deficient in DGKζ expression show reduced spine density and excitatory synaptic transmission. Time-lapse imaging indicates that DGKζ is required for spine maintenance but not formation. We propose that PSD-95 targets DGKζ to synaptic DAG-producing receptors to tightly couple synaptic DAG production to its conversion to PA for the maintenance of spine density.
ISSN
0261-4189
Language
English
URI
https://hdl.handle.net/10371/74034
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College of Dentistry/School of Dentistry (치과대학/치의학대학원)Dept. of Dentistry (치의학과)Journal Papers (저널논문_치의학과)
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