Synaptic removal of diacylglycerol by DGKzeta and PSD-95 regulates dendritic spine maintenance.
Published
Journal Article
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 DGKzeta is targeted to excitatory synapses through its direct interaction with the postsynaptic PDZ scaffold PSD-95. Overexpression of DGKzeta 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, DGKzeta knockdown reduces spine density. Mice deficient in DGKzeta expression show reduced spine density and excitatory synaptic transmission. Time-lapse imaging indicates that DGKzeta is required for spine maintenance but not formation. We propose that PSD-95 targets DGKzeta to synaptic DAG-producing receptors to tightly couple synaptic DAG production to its conversion to PA for the maintenance of spine density.
Full Text
Duke Authors
Cited Authors
- Kim, K; Yang, J; Zhong, X-P; Kim, M-H; Kim, YS; Lee, HW; Han, S; Choi, J; Han, K; Seo, J; Prescott, SM; Topham, MK; Bae, YC; Koretzky, G; Choi, S-Y; Kim, E
Published Date
- April 22, 2009
Published In
Volume / Issue
- 28 / 8
Start / End Page
- 1170 - 1179
PubMed ID
- 19229292
Pubmed Central ID
- 19229292
Electronic International Standard Serial Number (EISSN)
- 1460-2075
Digital Object Identifier (DOI)
- 10.1038/emboj.2009.44
Language
- eng
Conference Location
- England