Aspartyl Aminopeptidase Is Imported from the Cytoplasm to the Vacuole by Selective Autophagy in Saccharomyces cerevisiae*
Aspartyl Aminopeptidase Is Imported from the Cytoplasm to the Vacuole by Selective Autophagy in Saccharomyces cerevisiae*
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DOI：
10.1074/jbc.m110.173906
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发表时间：
2011-02
期刊：
影响因子：
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通讯作者：
Masaki Yuga;K. Gomi;D. Klionsky;T. Shintani
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文献类型：
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作者：
Masaki Yuga;K. Gomi;D. Klionsky;T. Shintani
大自噬是一种分解代谢过程，通过该过程，胞质组分被称为自噬体的双膜囊泡隔离，并被分选到溶酶体/空泡中进行降解。酿酒酵母已经将这种机制用于特定液泡水解酶氨肽酶I（Ape 1）和α-甘露糖苷酶（Ams 1）的组成型转运;该过程被称为细胞质至液泡靶向（Cvt）途径。Ape 1的前体形式在胞质溶胶中自组装成聚集体样结构，然后以前肽依赖性方式被Atg 19识别。Atg 19和自噬体形成机制之间的相互作用允许Ape 1-Atg 19复合物被自噬体样Cvt囊泡选择性包装。Ams 1还形成寡聚体，并通过与Atg 19相互作用利用Ape 1转运系统。虽然Cvt货物的选择性运输的机制已经得到了很好的研究，目前还不清楚是否通过Cvt途径转运蛋白以外的Ape 1和Ams 1。我们在这里描述，乙酰氨基肽酶（Yhr 113 w/Ape 4）是第三个Cvt货物，这是类似的一级结构和亚基组织Ape 1。Ape 4没有前肽，并且它不会自组装成聚集体。然而，它结合到Atg 19在一个网站不同于Ape 1和Ams 1结合位点，使其能够“背负”的Ape 1运输系统。在生长条件下，Ape 4的一小部分定位在液泡中，但其液泡运输被营养饥饿加速，并稳定地驻留在液泡腔中。我们建议，胞质Ape 4被重新分配到空泡时，酵母细胞需要更积极的空泡降解。
Macroautophagy is a catabolic process by which cytosolic components are sequestered by double membrane vesicles called autophagosomes and sorted to the lysosomes/vacuoles to be degraded. Saccharomyces cerevisiae has adapted this mechanism for constitutive transport of the specific vacuolar hydrolases aminopeptidase I (Ape1) and α-mannosidase (Ams1); this process is called the cytoplasm to vacuole targeting (Cvt) pathway. The precursor form of Ape1 self-assembles into an aggregate-like structure in the cytosol that is then recognized by Atg19 in a propeptide-dependent manner. The interaction between Atg19 and autophagosome-forming machineries allows selective packaging of the Ape1-Atg19 complex by the autophagosome-like Cvt vesicle. Ams1 also forms oligomers and utilizes the Ape1 transport system by interacting with Atg19. Although the mechanism of selective transport of the Cvt cargoes has been well studied, it is unclear whether proteins other than Ape1 and Ams1 are transported via the Cvt pathway. We describe here that aspartyl aminopeptidase (Yhr113w/Ape4) is the third Cvt cargo, which is similar in primary structure and subunit organization to Ape1. Ape4 has no propeptide, and it does not self-assemble into aggregates. However, it binds to Atg19 in a site distinct from the Ape1- and Ams1-binding sites, allowing it to “piggyback” on the Ape1 transport system. In growing conditions, a small portion of Ape4 localizes in the vacuole, but its vacuolar transport is accelerated by nutrient starvation, and it stably resides in the vacuole lumen. We propose that the cytosolic Ape4 is redistributed to the vacuole when yeast cells need more active vacuolar degradation.