Abstract
Phospholipase D2 (PLD2) is an enzyme that produces phosphatidic acid (PA), a lipid messenger molecule involved in a number of cellular events including, through its membrane curvature properties, endocytosis. The PLD2 knock out (PLD2KO) mouse has been previously reported to be protected from insult in a model of Alzheimer's disease. We have further analysed a PLD2KO mouse using mass spectrophotometry of its lipids and found significant differences in PA species throughout its brain. We have examined the expression pattern of PLD2 which allowed us to define which region of the brain to analyse for defect, notably PLD2 was not detected in glial-rich regions. The expression pattern lead us to specifically examine the mitral cells of olfactory bulbs, the Cornus Amonis (CA) regions of the hippocampus and the Purkinje cells of the cerebellum. We find that the change to longer PA species correlates with subtle architectural defect in the cerebellum, exemplified by ectopic Purkinje cells and an adult-onset deficit of olfaction. These observations draw parallels to defects in the reelin heterozygote as well as the effect of high fat diet on olfaction.
Highlights
Phospholipase D (PLD) is a signalling enzyme that catalyses the hydrolysis of the membrane lipid phosphatidylcholine (PC) to generate a soluble choline head group and the lipid phosphatidic acid (PA)[1,2,3]
To determine if the loss of Phospholipase D2 (PLD2) impacted upon the pool of phosphatidic acid lipids, either quantitatively or qualitatively, lipid mass spectrometry was adopted
The overall PA content relative to the main lipid content was not depleted in any region, suggesting that the activities of additional PA-producing enzymes, for example PLD1, can compensate for the absence of PLD2-produced PA
Summary
Phospholipase D (PLD) is a signalling enzyme that catalyses the hydrolysis of the membrane lipid phosphatidylcholine (PC) to generate a soluble choline head group and the lipid phosphatidic acid (PA)[1,2,3]. With its small negatively-charged head group and two large acyl chains that confer a “cone-like” morphology, PA triggers a conformational change in the membrane that results in local negative folding. PA is a bioactive lipid that regulates protein position by attracting their positively charged PA-binding domains to the membrane, and sometimes modulates their activity [4,5,6]. The PLD gene family comprises six members, only PLD1 and PLD2 have been clearly demonstrated to hydrolyse PC. PLOS ONE | DOI:10.1371/journal.pone.0162814 September 22, 2016
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