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

Diacylglycerol kinase (DGK) is an enzyme that phosphorylates diacylglycerol to phosphatidic acid and comprises multiple isozymes of distinct properties. Of DGKs, mRNA signal for DGKbeta is strongly detected in the striatum, and one of the transcripts derived from the human DGKbeta locus is annotated in GenBank as being differentially expressed in bipolar disorder patients. Recently, we have reported that DGKbeta is expressed in medium spiny neurons of the striatum and is highly concentrated at the perisynapse of dendritic spines. However, it remains elusive how DGKbeta is implicated in pathophysiological role in neurons at the cellular level.

In the present study, we investigated the expression and subcellular localization of DGKbeta in the hippocampus, together with its functional implication using transfected hippocampal neurons. DGKbeta is expressed not only in projection neurons but also in interneurons and is concentrated at perisynaptic sites of asymmetrical synapses. Overexpression of wild-type DGKbeta 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.

In the hippocampus, DGKbeta is expressed in both projection neurons and interneurons and is accumulated at the perisynapse of dendritic spines in asymmetrical synapses. Transfection experiments suggest that DGKbeta may be involved in the molecular machineries of dendrite outgrowth and spinogenesis through its kinase activity.