The phospholipase D1 pathway modulates macroautophagy Journal Article
| Authors: | Dall'Armi, C.; Hurtado-Lorenzo, A.; Tian, H.; Morel, E.; Nezu, A.; Chan, R. B.; Yu, W. H.; Robinson, K. S.; Yeku, O.; Small, S. A.; Duff, K.; Frohman, M. A.; Wenk, M. R.; Yamamoto, A.; Di Paolo, G. |
| Article Title: | The phospholipase D1 pathway modulates macroautophagy |
| Abstract: | 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. © 2010 Macmillan Publishers Limited. All rights reserved. |
| Keywords: | nonhuman; protein function; protein blood level; animal cell; mouse; animal tissue; cell structure; enzyme inhibition; animal experiment; animal model; enzyme activity; regulatory mechanism; autophagy; phagosome; enzyme localization; wortmannin; downstream processing; protein p62; tau protein; modulation; phosphatidylinositol 3 kinase inhibitor; starvation; phospholipase d1; enzyme blood level; outer membrane |
| Journal Title: | Nature Communications |
| Volume: | 1 |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2010-01-01 |
| Start Page: | 142 |
| Language: | English |
| DOI: | 10.1038/ncomms1144 |
| PROVIDER: | scopus |
| PUBMED: | 21266992 |
| PMCID: | PMC3328354 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 20 April 2011" - "Art. No.: 142" - "Source: Scopus" |
