The phospholipase D1 pathway modulates macroautophagy

被引：131

作者：

Dall'Armi, Claudia ^{[1
,2
]}

Hurtado-Lorenzo, Andres ^{[1
,2
]}

Tian, Huasong ^{[1
,2
]}

Morel, Etienne ^{[1
,2
]}

Nezu, Akiko ^{[3
]}

Chan, Robin B. ^{[1
,2
]}

Yu, W. Haung ^{[1
,2
]}

Robinson, Kimberly S. ^{[1
,2
]}

Yeku, Oladapo ^{[4
,5
]}

Small, Scott A. ^{[2
,6
]}

Duff, Karen ^{[1
,2
]}

Frohman, Michael A. ^{[4
,5
]}

Wenk, Markus R. ^{[7
,8
]}

Yamamoto, Akitsugu ^{[3
]}

Di Paolo, Gilbert ^{[1
,2
]}

机构：

[1] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10032 USA

[2] Columbia Univ, Med Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY 10032 USA

[3] Nagahama Inst Biosci & Technol, Dept Anim Biosci, Fac Biosci, Shiga 5260829, Japan

[4] SUNY Stony Brook, Ctr Dev Genet, Stony Brook, NY 11794 USA

[5] SUNY Stony Brook, Dept Pharmacol, Stony Brook, NY 11794 USA

[6] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA

[7] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biochem, Singapore 117597, Singapore

[8] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Biol Sci, Singapore 117543, Singapore

来源：

NATURE COMMUNICATIONS | 2010年 / 1卷

基金：

英国医学研究理事会; 新加坡国家研究基金会;

关键词：

AUTOPHAGOSOME FORMATION; PHOSPHATIDIC-ACID; PROTEIN; FUSION; MTOR; DISEASE; PHOSPHOINOSITIDES; NEURODEGENERATION; COORDINATION; SECRETION;

D O I：

10.1038/ncomms1144

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：11

共 57 条

[11] Regulation of phospholipase D1 subcellular cycling through coordination of multiple membrane association motifs [J].