Diacylglycerol kinase β promotes dendritic outgrowth and spine maturation in developing hippocampal neurons

Background: Diacylglycerol kinase (DGK) is an enzyme that phosphorylates diacylglycerol to phosphatidic acid and comprises multiple isozymes of distinct properties. Of DGKs, mRNA signal for DGK beta is strongly detected in the striatum, and one of the transcripts derived from the human DGK beta locus is annotated in GenBank as being differentially expressed in bipolar disorder patients. Recently, we have reported that DGK beta is expressed in medium spiny neurons of the striatum and is highly concentrated at the perisynapse of dendritic spines. However, it remains elusive how DGK beta is implicated in pathophysiological role in neurons at the cellular level. Results: In the present study, we investigated the expression and subcellular localization of DGK beta in the hippocampus, together with its functional implication using transfected hippocampal neurons. DGK beta is expressed not only in projection neurons but also in interneurons and is concentrated at perisynaptic sites of asymmetrical synapses. Overexpression of wild-type DGK beta promotes dendrite outgrowth at 7 d in vitro (DIV) and spine maturation at 14 DIV in transfected hippocampal neurons, although its kinase-dead mutant has no effect. Conclusion: In the hippocampus, DGK beta is expressed in both projection neurons and interneurons and is accumulated at the perisynapse of dendritic spines in asymmetrical synapses. Transfection experiments suggest that DGK beta may be involved in the molecular machineries of dendrite outgrowth and spinogenesis through its kinase activity.