Phosphatidic acid and neurotransmission

Abstract

Lipids play a vital role in the health and functioning of neurons and interest in the physiological role of neuronal lipids is certainly increasing. One neuronal function in which neuronal lipids appears to play key roles in neurotransmission. Our understanding of the role of lipids in the synaptic vesicle cycle and neurotransmitter release is becoming increasingly more important. Much of the initial research in this area has highlighted the major roles played by the phosphoinositides (PtdIns), diacylglycerol (DAG), and phosphatidic acid (PtdOH). Of these, PtdOH has not received as much attention as the other lipids although its role and metabolism appears to be extremely important. This lipid has been shown to play a role in modulating both exocytosis and endocytosis although its precise role in either process is not well defined. The currently evidence suggest this lipid likely participates in key processes by altering membrane architecture necessary for membrane fusion, mediating the penetration of membrane proteins, serving as a precursor for other important SV cycling lipids, or activating essential enzymes. In this review, we address the sources of PtdOH, the enzymes involved in its production, the regulation of these enzymes, and its potential roles in neurotransmission in the central nervous system.

Figure 1. Sources of Phosphatidic Acid

PtdIns(4,5)P₂ = phosphatidylinositol-4,5-bisphosphate; PtdOH = phosphatidic acid; lysPtdOH = lysophosphatidic acid; PtdCho = phosphatidylcholine; DGK = diacyglycerol kinase; PLD = phospholipase D; PLC = phospholipase C; LPAAT = lysophosphatidic acid acyltransferase.

Figure 2

Proposed Roles of PLD1 and DGK-θ Generated PtdOH in the SV Exocytosis and Endocytosis.