Regulation and roles of neuronal diacylglycerol kinases: a lipid perspective

Crit Rev Biochem Mol Biol. 2011 Oct;46(5):353-64. doi: 10.3109/10409238.2011.577761. Epub 2011 May 4.

Abstract

Diacylglycerol kinases (DGKs) are a class of enzymes that catalyze the ATP-dependent conversion of diacylglycerol (DAG) to phosphatidic acid (PtdOH), resulting in the coordinate regulation of these two lipid second messengers. This regulation is particularly important in the nervous system where it is now well-established that DAG and PtdOH serve very important roles in modulating a variety of neurological functions. There are currently 10 identified mammalian DGKs, organized into five classes or "Types" based upon similarities in their primary sequences. A number of studies have identified eight of these isoforms in various regions of the mammalian central nervous system (CNS): DGK-α, DGK-β, DGK-γ, DGK-η, DGK-ζ, DGK-ι, DGK-ϵ, and DGK-θ. Further studies have provided compelling evidence supporting roles for these enzymes in neuronal spine density, myelination, synaptic activity, neuronal plasticity, epileptogenesis and neurotransmitter release. The physiological regulation of these enzymes is less clear. Like all interfacial enzymes, DGKs metabolize their hydrophobic substrate (DAG) at a membrane-aqueous interface. Therefore, these enzymes can be regulated by alterations in their subcellular localization, enzymatic activity, and/or membrane association. In this review, we summarize what is currently understood about the localization and regulation of the neuronal DGKs in the mammalian CNS.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / enzymology*
  • Central Nervous System / enzymology*
  • Central Nervous System / metabolism
  • Diacylglycerol Kinase / chemistry
  • Diacylglycerol Kinase / classification
  • Diacylglycerol Kinase / metabolism*
  • Diglycerides / metabolism
  • Enzyme Activation
  • Gene Expression Regulation
  • Humans
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Lipid Metabolism*
  • Neurons / enzymology*
  • Phosphatidic Acids / metabolism

Substances

  • Diglycerides
  • Isoenzymes
  • Phosphatidic Acids
  • Diacylglycerol Kinase