Expression of a ULK1/2 binding-deficient ATG13 variant can partially restore autophagic activity in ATG13-deficient cells

被引：69

作者：

Hieke, Nora ^{[1
]}

Loeffler, Antje S. ^{[1
]}

Kaizuka, Takeshi ^{[2
,3
,4
]}

Berleth, Niklas ^{[1
]}

Boehler, Philip ^{[1
]}

Driessen, Stefan ^{[1
]}

Stuhldreier, Fabian ^{[1
]}

Friesen, Olena ^{[1
]}

Assani, Kaivon ^{[5
]}

Schmitz, Katharina ^{[1
]}

Peter, Christoph ^{[1
]}

Diedrich, Britta ^{[6
]}

Dengjel, Joern ^{[6
]}

Holland, Petter ^{[7
]}

Simonsen, Anne ^{[7
]}

Wesselborg, Sebastian ^{[1
]}

Mizushima, Noboru ^{[2
,3
,4
]}

Stork, Bjoern ^{[1
]}

机构：

[1] Univ Dusseldorf, Inst Mol Med 1, Dusseldorf, Germany

[2] Univ Tokyo, Dept Biochem & Mol Biol, Grad Sch, Tokyo, Japan

[3] Univ Tokyo, Fac Med, Tokyo, Japan

[4] Tokyo Med & Dent Univ, Dept Physiol & Cell Biol, Tokyo, Japan

[5] Childrens Hosp, Res Inst Nationwide, Ctr Microbial Pathogenesis, Columbus, OH 43205 USA

[6] Univ Freiburg, Dept Dermatol, ZBSA Ctr Biol Syst Analysis,Med Ctr, BIOSS Ctr Biol Signaling Studies,Freiburg Inst Ad, Freiburg, Germany

[7] Univ Oslo, Inst Basic Med Sci, Fac Med, Oslo, Norway

来源：

AUTOPHAGY | 2015年 / 11卷 / 09期

基金：

日本学术振兴会;

关键词：

ATG13; ATG101; autophagy; RB1CC1; ULK1; PDZ DOMAINS; COMPLEX; PROTEIN; PHOSPHORYLATION; KINASE; AMPK; ASSOCIATION; INTERACTS; PARTNERS; AMBRA1;

D O I：

10.1080/15548627.2015.1068488

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Autophagy describes an intracellular process responsible for the lysosome-dependent degradation of cytosolic components. The ULK1/2 complex comprising the kinase ULK1/2 and the accessory proteins ATG13, RB1CC1, and ATG101 has been identified as a central player in the autophagy network, and it represents the main entry point for autophagy-regulating kinases such as MTOR and AMPK. It is generally accepted that the ULK1 complex is constitutively assembled independent of nutrient supply. Here we report the characterization of the ATG13 region required for the binding of ULK1/2. This binding site is established by an extremely short peptide motif at the C terminus of ATG13. This motif is mandatory for the recruitment of ULK1 into the autophagy-initiating high-molecular mass complex. Expression of a ULK1/2 binding-deficient ATG13 variant in ATG13-deficient cells resulted in diminished but not completely abolished autophagic activity. Collectively, we propose that autophagy can be executed by mechanisms that are dependent or independent of the ULK1/2-ATG13 interaction.

引用

页码：1471 / 1483

页数：13

共 39 条

[1]

Atg13 and FIP200 act independently of Ulk1 and Ulk2 in autophagy induction [J].