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.

Phosphatidic acid in membrane rearrangements

“…Another pathway is the acylation of DHAP to 1‐acyl‐DHAP (Ac‐DHAP) via DHAP acyltransferase (DHAP AT), followed by the reduction of Ac‐DHAP to LPA via Ac‐DHAP reductase . the phosphorylation of diacylglycerol (DAG) by diacylglycerol kinases (DGKs) . Ten members of DGK family are known ( and references therein); hydrolysis of phospholipids by phospholipase D (PLD) . Among the six known PLD isoforms, the mammalian PLD1 and PLD2 are the best studied ( and references therein).…”

“…Ten members of DGK family are known ( and references therein); hydrolysis of phospholipids by phospholipase D (PLD) . Among the six known PLD isoforms, the mammalian PLD1 and PLD2 are the best studied ( and references therein). PLD6 (MitoPLD) generates PA via hydrolysis of cardiolipin on the outer surface of the mitochondria .…”

“…2 the phosphorylation of diacylglycerol (DAG) by diacylglycerol kinases (DGKs) [32][33][34]. Ten members of DGK family are known ( [13] and references therein); 3 hydrolysis of phospholipids by phospholipase D (PLD) [1,[35][36][37][38][39]. Among the six known PLD isoforms, the mammalian PLD1 and PLD2 are the best studied ( [13,39] and references therein).…”

Soy Lecithin-Derived Phosphatidylserine Plus Phosphatidic Acid: Effects on Brain Functions in Elderly Patients with Alzheimer's Disease and Dementia

“…PA is not only a precursor for other phospholipids, but also plays a pivotal role by influencing membrane fluidity, which is especially important for vesicle formation, e.g. during neurotransmission [42]. However there is only limited clinical evidence regarding PA supplementation in elderly people with dementia or age associated memory impairment.…”

Phosphatidic acid metabolism regulates neuroendocrine secretion but is not under the direct control of lipins

“…PLD1‐dependent PA synthesis was also reported to be required for efficient secretion of insulin from β‐pancreatic cells, von Willebrand factor from endothelial cells, acrosomal exocytosis from sperm cells, and neurotransmitter release . Supporting the notion that PA is required for neurotransmission, different enzymes controlling PA metabolism such as PLDs, lysophosphatidic acid acyltransferases (LPAATs), and diacylglycerol (DAG)‐kinases (DGKs) were subsequently implicated in neurotransmitter release in various neuronal model systems . Yet, besides the formation of PA observed in the vicinity of the release sites, to date, there is still little information regarding the dynamics of PA synthesis and catabolism during secretion.…”