Early Steps in Autophagy Depend on Direct Phosphorylation of Atg9 by the Atg1 Kinase

被引：346

作者：

Papinski, Daniel ^{[1
]}

Schuschnig, Martina ^{[1
]}

Reiter, Wolfgang ^{[1
]}

Wilhelm, Larissa ^{[1
]}

Barnes, Christopher A. ^{[2
]}

Maiolica, Alessio ^{[2
]}

Hansmann, Isabella ^{[1
]}

Pfaffenwimmer, Thaddaeus ^{[1
]}

Kijanska, Monika ^{[3
]}

Stoffel, Ingrid ^{[3
]}

Lee, Sung Sik ^{[3
]}

Brezovich, Andrea ^{[1
]}

Lou, Jane Hua ^{[4
]}

Turk, Benjamin E. ^{[4
]}

Aebersold, Ruedi ^{[2
]}

Ammerer, Gustav ^{[1
]}

Peter, Matthias ^{[3
]}

Kraft, Claudine ^{[1
]}

机构：

[1] Univ Vienna, Max F Perutz Labs, A-1030 Vienna, Austria

[2] ETH, Inst Mol Syst Biol, Dept Biol, CH-8093 Zurich, Switzerland

[3] ETH, Dept Biol, Inst Biochem, CH-8093 Zurich, Switzerland

[4] Yale Univ Sch Med, Dept Pharmacol, New Haven, CT 06520 USA

来源：

MOLECULAR CELL | 2014年 / 53卷 / 03期

基金：

奥地利科学基金会; 美国国家卫生研究院; 欧洲研究理事会; 瑞士国家科学基金会;

关键词：

SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; BETA-PROPELLER; CVT PATHWAY; C-ELEGANS; IN-VIVO; YEAST; CYTOPLASM; COMPLEX; SPECIFICITY;

D O I：

10.1016/j.molcel.2013.12.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Bulk degradation of cytoplasmic material is mediated by a highly conserved intracellular trafficking pathway termed autophagy. This pathway is characterized by the formation of double-membrane vesicles termed autophagosomes engulfing the substrate and transporting it to the vacuole/lysosorne for breakdown and recycling. The Atg1/ULK1 kinase is essential for this process; however, little is known about its targets and the means by which it controls autophagy. Here we have screened for Atg1 kinase substrates using consensus peptide arrays and identified three components of the autophagy machinery. The multimembrane-spanning protein Atg9 is a direct target of this kinase essential for autophagy. Phosphorylated Atg9 is then required for the efficient recruitment of Atg8 and Atg18 to the site of autophagosome formation and subsequent expansion of the isolation membrane, a prerequisite for a functioning autophagy pathway. These findings show that the Atg1 kinase acts early in autophagy by regulating the outgrowth of autophagosomal membranes.

引用

页码：471 / 483

页数：13

共 40 条

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