Reggiori Fulvio, Tucker Katherine A, Stromhaug Per E, Klionsky Daniel J
Life Sciences Institute and Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Dev Cell. 2004 Jan;6(1):79-90. doi: 10.1016/s1534-5807(03)00402-7.
To survive extreme environmental conditions, and in response to certain developmental and pathological situations, eukaryotic organisms employ the catabolic process of autophagy. Structures targeted for destruction are enwrapped by double-membrane vesicles, then delivered into the interior of the lysosome/vacuole. Despite the identification of many specific components, the molecular mechanism that directs formation of the sequestering vesicles remains largely unknown. We analyzed the trafficking of Atg23 and the integral membrane protein Atg9 in the yeast Saccharomyces cerevisiae. These components localize both to the pre-autophagosomal structure (PAS) and other cytosolic punctate compartments. We show that Atg9 and Atg23 cycle through the PAS in a process governed by the Atg1-Atg13 signaling complex. Atg1 kinase activity is essential only for retrograde transport of Atg23, while recycling of Atg9 requires additional factors including Atg18 and Atg2. We postulate that Atg9 employs a recycling system mechanistically similar to that used at yeast early and late endosomes.
为了在极端环境条件下生存，并应对某些发育和病理情况，真核生物会采用自噬这一分解代谢过程。被靶向破坏的结构会被双膜囊泡包裹，然后被递送至溶酶体/液泡内部。尽管已经鉴定出许多特定成分，但指导隔离囊泡形成的分子机制在很大程度上仍然未知。我们分析了酿酒酵母中Atg23和整合膜蛋白Atg9的运输情况。这些成分定位于自噬前体结构（PAS）和其他胞质点状区室。我们发现，Atg9和Atg23在由Atg1-Atg13信号复合体控制的过程中通过PAS循环。Atg1激酶活性仅对Atg23的逆行运输至关重要，而Atg9的循环需要包括Atg18和Atg2在内的其他因子。我们推测，Atg9采用了一种在机制上类似于酵母早期和晚期内体所使用的循环系统。
