Phospholipase D

The phospholipase D (PLD) enzymatic superfamily performs transphosphatidylation reactions on varied substrates containing phosphodiester bonds. PLD family members are best known for using this mechanism to hydrolyze the abundant membrane lipid phosphatidylcholine to generate phosphatidic acid (PA), a potent lipid second messenger. More eclectic PLDs hydrolyze other lipids to generate PA, function as DNAses by hydrolyzing DNA backbone phosphodiester bonds, rescue stalled topoisomerase-DNA complexes by severing DNA-protein phosphodiester linkages, or synthesize new lipids by using a lipid donor instead of water to perform the transphosphatidylation reaction. PA has multiple mechanisms through which it affects cellular function, including acting as a lipid anchor to recruit proteins to specific subcellular locations, activating other enzymes, altering membrane shape, or serving as substrate to generate other signaling or bioactive lipids. PLDs are found in bacteria, poxviruses, yeast, plants, and animals, where they help regulate processes such as membrane vesicle trafficking and changes in cell shape, but in general are not intrinsically essential for the processes or for viability. Nonetheless, PLDs play critical roles in pathogenicity for poxviruses and some bacteria, in yeast sporulation, in Drosophila phototransduction, and in mammalian platelet activation and neutrophil migration, underscoring the varied physiological processes connected to this signaling pathway.