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Synaptic removal of diacylglycerol by DGKζ and PSD‐95 regulates dendritic spine maintenance
Author(s) -
Kim Karam,
Yang Jinhee,
Zhong XiaoPing,
Kim MyoungHwan,
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 SeYoung,
Kim Eunjoon
Publication year - 2009
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.44
Subject(s) - diacylglycerol kinase , dendritic spine , biology , excitatory postsynaptic potential , postsynaptic density , microbiology and biotechnology , neurotransmission , synapse , scaffold protein , postsynaptic potential , retrograde signaling , kinase , neuroscience , signal transduction , biochemistry , receptor , inhibitory postsynaptic potential , protein kinase c , hippocampal formation
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.