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Publication : The phospholipase D1 pathway modulates macroautophagy.

First Author  Dall'Armi C Year  2010
Journal  Nat Commun Volume  1
Pages  142 PubMed ID  21266992
Mgi Jnum  J:207283 Mgi Id  MGI:5555015
Doi  10.1038/ncomms1144 Citation  Dall'Armi C, et al. (2010) The phospholipase D1 pathway modulates macroautophagy. Nat Commun 1:142
abstractText  Although macroautophagy is known to be an essential degradative process whereby autophagosomes mediate the engulfment and delivery of cytoplasmic components into lysosomes, the lipid changes underlying autophagosomal membrane dynamics are undetermined. Here, we show that phospholipase D1 (PLD1), which is primarily associated with the endosomal system, partially relocalizes to the outer membrane of autophagosome-like structures upon nutrient starvation. The localization of PLD1, as well as the starvation-induced increase in PLD activity, are altered by wortmannin, a phosphatidylinositol 3-kinase inhibitor, suggesting PLD1 may act downstream of Vps34. Pharmacological inhibition of PLD and genetic ablation of PLD1 in mouse cells decreased the starvation-induced expansion of LC3-positive compartments, consistent with a role of PLD1 in the regulation of autophagy. Furthermore, inhibition of PLD results in higher levels of Tau and p62 aggregates in organotypic brain slices. Our in vitro and in vivo findings establish a role for PLD1 in autophagy.
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