@article {pmid21347278,
	title = {Srf1 is a novel regulator of phospholipase D activity and is essential to buffer the toxic effects of C16:0 platelet activating factor},
	journal = {PLoS Genet.},
	volume = {7},
	number = {2},
	year = {2011},
	pages = {e1001299},
	abstract = {During Alzheimer{\textquoteright}s Disease, sustained exposure to amyloid-{\^I}{\texttwosuperior}{\^a}{\quotesinglbase}{\quotedblbase}{\^a}{\quotesinglbase}{\quotesinglbase} oligomers perturbs metabolism of ether-linked glycerophospholipids defined by a saturated 16 carbon chain at the sn-1 position. The intraneuronal accumulation of 1-O-hexadecyl-2-acetyl-sn-glycerophosphocholine (C16:0 PAF), but not its immediate precursor 1-O-hexadecyl-sn-glycerophosphocholine (C16:0 lyso-PAF), participates in signaling tau hyperphosphorylation and compromises neuronal viability. As C16:0 PAF is a naturally occurring lipid involved in cellular signaling, it is likely that mechanisms exist to protect cells against its toxic effects. Here, we utilized a chemical genomic approach to identify key processes specific for regulating the sensitivity of Saccharomyces cerevisiae to alkyacylglycerophosphocholines elevated in Alzheimer{\textquoteright}s Disease. We identified ten deletion mutants that were hypersensitive to C16:0 PAF and five deletion mutants that were hypersensitive to C16:0 lyso-PAF. Deletion of YDL133w, a previously uncharacterized gene which we have renamed SRF1 (Spo14 Regulatory Factor 1), resulted in the greatest differential sensitivity to C16:0 PAF over C16:0 lyso-PAF. We demonstrate that Srf1 physically interacts with Spo14, yeast phospholipase D (PLD), and is essential for PLD catalytic activity in mitotic cells. Though C16:0 PAF treatment does not impact hydrolysis of phosphatidylcholine in yeast, C16:0 PAF does promote delocalization of GFP-Spo14 and phosphatidic acid from the cell periphery. Furthermore, we demonstrate that, similar to yeast cells, PLD activity is required to protect mammalian neural cells from C16:0 PAF. Together, these findings implicate PLD as a potential neuroprotective target capable of ameliorating disruptions in lipid metabolism in response to accumulating oligomeric amyloid-{\^I}{\texttwosuperior}{\^a}{\quotesinglbase}{\quotedblbase}{\^a}{\quotesinglbase}{\quotesinglbase}.},
	author = {Kennedy, M. A. and Kabbani, N. and Lambert, J. P. and Swayne, L. A. and Ahmed, F. and Figeys, D. and Bennett, S. A. and Bryan, J. and Baetz, K.}
}
