Self-Interaction Is Critical for Atg9 Transport and Function at the Phagophore Assembly Site during Autophagy
Self-Interaction Is Critical for Atg9 Transport and Function at the Phagophore Assembly Site during Autophagy
复制标题
DOI：
10.1091/mbc.e08-05-0544
复制
发表时间：
2008-12-01
影响因子：
3.3
通讯作者：
Klionsky, Daniel J.
中科院分区：
文献类型：
--
作者：
He, Congcong;Baba, Misuzu;Klionsky, Daniel J.
自噬是细胞自身成分在溶酶体（或类似的酵母液泡）内的降解，其功能障碍导致多种人类疾病。Atg9是唯一的完整的膜蛋白所需的初始隔离室，吞噬细胞的形成，并提出了在膜运输中发挥关键作用，吞噬细胞推测扩大囊泡除了形成一个完整的自噬体。目前尚不清楚Atg9在吞噬细胞组装位点（PAS）发挥作用的机制。在这里，我们报告说，Atg9分子自我关联独立于其他已知的自噬蛋白在营养丰富和饥饿条件。突变分析表明，自我相互作用是至关重要的顺行运输的Atg9 PAS。Atg 9自我相互作用的能力是PAS吞噬细胞扩张步骤中选择性和非选择性自噬所必需的。我们的研究结果支持一个模型，其中Atg9多聚化促进膜流PAS吞噬细胞的形成。
Autophagy is the degradation of a cell's own components within lysosomes (or the analogous yeast vacuole), and its malfunction contributes to a variety of human diseases. Atg9 is the sole integral membrane protein required in formation of the initial sequestering compartment, the phagophore, and is proposed to play a key role in membrane transport; the phagophore presumably expands by vesicular addition to form a complete autophagosome. It is not clear through what mechanism Atg9 functions at the phagophore assembly site (PAS). Here we report that Atg9 molecules self-associate independently of other known autophagy proteins in both nutrient-rich and starvation conditions. Mutational analyses reveal that self-interaction is critical for anterograde transport of Atg9 to the PAS. The ability of Atg9 to self-interact is required for both selective and nonselective autophagy at the step of phagophore expansion at the PAS. Our results support a model in which Atg9 multimerization facilitates membrane flow to the PAS for phagophore formation.