Phospholipid signalling through phospholipase D and phosphatidic acid

Abstract

SummaryPhospholipase D (PLD) hydrolyzes the phosphodiester bond of the predominant membrane phospholipid, phosphatidylcholine producing phosphatidic acid and free choline. This activity can participate in signal transduction pathways and impact on vesicle trafficking for secretion and endocytosis, as well as receptor signalling. Phospholipids can regulate PLD activity directly, through specific intermolecular interactions, or indirectly, through their effect on the localization or activity of PLD's protein effectors. This short review highlights these various phospholipid inputs into the regulation of PLD activity and also reviews potential roles for PLD-generated phosphatidic acid, particularly a mechanism by which the phospholipid may participate in the process of vesicular trafficking.

The Role of Phospholipase D in Regulated Exocytosis

“…membrane microdomains defining the physiological fusion machine) (18,19,33). On the other hand, a substantially higher level of PM PLD activity is perhaps not surprising considering the multiple functions now attributed to PA (1)(2)(3)(4)(5)(6). The data suggest that the profound suppression of fusion extent and kinetics seen for ex vivo incubations with PLD inhibitors (i.e.…”

“…a minor component of the membrane, PA is a biologically active lipid involved in regulated exocytosis, trafficking, membrane dynamics, and responses to environmental stimuli (1)(2)(3)(4)(5)(6). PA is also involved in the activation of sphingosine kinase, which is known to modulate intracellular Ca 2ϩ -release in neutrophils (7)(8)(9) and to activate proteins responsible for cell survival, including mTOR (10), Hsp22 (11), and Ras (12).…”

Lysophosphatidic Acid Induces Interleukin-13 (IL-13) Receptor α2 Expression and Inhibits IL-13 Signaling in Primary Human Bronchial Epithelial Cells

“…The PLD isoenzymes PLD1 and PLD2 catalyze the hydrolysis of the phosphodiester bond of glycerophospholipids to generate phosphatidic acid and a free head group and are activated by hormones, growth factors, neurotransmitters, cytokines, and reactive oxygen species (52,53). PLD is a critical enzyme in intracellular signal transduction.…”

Developmental phases of individual mouse preimplantation embryos characterized by lipid signatures using desorption electrospray ionization mass spectrometry

“…Phospholipids (PL), the major class of cellular lipids, constitute cell membranes and are involved in key cell signaling events [14,15]. A 13-fold increase in phosphocholine (PCho) synthesis in mouse embryos from the two-to eight-cell stages has been previously reported by supplementing the culture medium with labeled choline (methyl-3H-choline) as a lipid precursor, suggesting not only membrane synthesis activity but also membrane remodeling during preimplantation development [16].…”