Dual role of Atg1 in regulation of autophagy-specific PAS assembly in Saccharomyces cerevisiae
Dual role of Atg1 in regulation of autophagy-specific PAS assembly in Saccharomyces cerevisiae
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DOI：
10.4161/auto.6375
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发表时间：
2008-07-01
期刊：
影响因子：
13.3
通讯作者：
Klionsky, Daniel J.
中科院分区：
文献类型：
--
作者：
Cheong, Hessun;Klionsky, Daniel J.
大多数自噬相关（Atg）蛋白在吞噬体组装位点或前自噬体结构（PAS）处组装，这是在营养或饥饿条件下形成囊泡的潜在位点。为了了解囊泡形成的初始步骤，重要的是要知道Atg蛋白是如何被招募到PAS的。Atg11促进PAS组装细胞质液泡靶向（Cvt）途径在营养条件下。为了检查自噬特异性PAS形成，使用ATG11缺失突变体来消除在营养条件下发生的PAS形成。我们发现，Atg1，Atg13和Atg17在自噬诱导条件下对PAS形成起着类似的作用，这与Atg11在营养生长过程中所起的作用相似。特别是，Atg1被认为在自噬特异性PAS募集中具有双重作用。Atg1在将Atg蛋白有效募集至PAS中起着结构性作用，其通过与Atg13和Atg17的相互作用介导。相比之下，Atg 1激酶活性是在自噬诱导条件下Atg蛋白从PAS解离所必需的，该功能对于自噬活性也是至关重要的。
Most autophagy-related (Atg) proteins are assembled at the phagophore assembly site or pre-autophagosomal structure (PAS), which is a potential site for vesicle formation during vegetative or starvation conditions. To understand the initial step of vesicle formation, it is important to know how Atg proteins are recruited to the PAS. Atg11 facilitates PAS assembly for the cytoplasm to vacuole targeting (Cvt) pathway in vegetative conditions. To examine autophagy-specific PAS formation, an ATG11 deletion mutant was used to eliminate the PAS formation that occurs in vegetative conditions. We found that Atg1, Atg13 and Atg17 play a similar role for PAS formation under autophagy-inducing conditions as seen for Atg11 during vegetative growth. In particular, Atg1 is proposed to have dual roles for autophagy-specific PAS recruitment. Atg1 plays a structural role for efficient recruitment of Atg proteins to the PAS, which is mediated by interaction with Atg13 and Atg17. In contrast, Atg1 kinase activity is needed for dissociation of Atg proteins from the PAS during autophagy inducing conditions, a function which is also critical for autophagy activity.