Diacylglycerol kinases in the regulation of dendritic spines

Abstract

Diacylglycerol (DAG) is an important lipid-signaling molecule that binds and activates various downstream effectors. Tight control over the production and removal of DAG is important in maintaining the dynamic responses of the DAG signaling system to a changing environment. Diacylglycerol kinases (DGKs) are enzymes that convert DAG to phosphatidic acid (PA). This conversion terminates DAG signaling and, at the same time, initiates additional signaling events downstream of PA, which also acts as a lipid-signaling molecule. However, little is known about how (or if) DGKs are targeted to specific subcellular sites or how DGKs tightly regulate local DAG and PA signaling. Dendritic spines are tiny protrusions on neuronal dendrites that receive the majority of excitatory synaptic inputs. They are also the sites where DAG molecules are produced through activation of postsynaptic receptors, including metabotropic glutamate receptors and NMDA receptors. Accumulating evidence indicates that synaptic levels of DAG and PA are important determinants of dendritic spine stability and that the DGKzeta isoform at excitatory postsynaptic sites is critically involved in spine maintenance. In addition, DGKzeta appears to form a multi-protein complex with functionally related proteins to organize efficient DAG and PA signaling pathways at excitatory synapses.