Expression of a ULK1/2 binding-deficient ATG13 variant can partially restore autophagic activity in ATG13-deficient cells
Expression of a ULK1/2 binding-deficient ATG13 variant can partially restore autophagic activity in ATG13-deficient cells
复制标题
DOI：
10.1080/15548627.2015.1068488
复制
发表时间：
2015-09-01
期刊：
影响因子：
13.3
通讯作者：
Stork, Bjoern
中科院分区：
文献类型：
--
作者：
Hieke, Nora;Loeffler, Antje S.;Stork, Bjoern
自噬描述了一种细胞内的过程，负责溶酶体依赖性降解的胞质组分。由激酶ULK 1/2和辅助蛋白ATG 13、RB 1CC 1和ATG 101组成的ULK 1/2复合物已被鉴定为自噬网络中的中心参与者，它代表了自噬调节激酶如MTOR和AMPK的主要入口点。一般认为ULK 1复合物的组成型组装不依赖于营养供应。在这里，我们报告的ATG 13区域所需的ULK 1/2的结合特性。该结合位点由ATG 13的C末端的极短肽基序建立。该基序对于将ULK 1募集到自噬起始的高分子量复合物中是必需的。在ATG 13缺陷细胞中表达ULK 1/2结合缺陷的ATG 13变体导致自噬活性降低但未完全消除。总的来说，我们提出自噬可以通过依赖或独立于ULK 1/2-ATG 13相互作用的机制来执行。
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.