YGR198w (YPP1) targets A30P alpha-synuclein to the vacuole for degradation.
YGR198w (YPP1) targets A30P alpha-synuclein to the vacuole for degradation.
复制标题
YGR198W（YPP1）将A30Pα-突触核蛋白靶向液泡以进行降解。
DOI：
10.1083/jcb.200610071
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发表时间：
2007-06-18
影响因子：
7.8
通讯作者：
Witt, Stephan N
中科院分区：
文献类型：
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作者：
Flower, Todd R;Clark-Dixon, Cheryl;Metoyer, Cheynita;Yang, Hui;Shi, Runhua;Zhang, Zhaojie;Witt, Stephan N
使用遗传筛选，我们发现YGR 198 w（命名为YPP 1），这是一种功能未知的酿酒酵母必需基因，抑制与早发性帕金森病相关的α-突触核蛋白（α-syn）突变体（A30 P）的毒性。在这里，我们发现YPP 1抑制A30 P的致死性，但不抑制野生型α-syn或A53 T突变体的致死性。当Ypp 1蛋白过度表达时，三种α-syns中的每一种都会进入从质膜上出芽的囊泡，但只有含有A30 P的囊泡会进入液泡并与液泡合并，在液泡中A30 P被蛋白水解降解。我们表明Ypp 1 p与A30 P结合，但不与其他两个α-syns结合; YPP 1与参与内吞/肌动蛋白动力学（SLA 1、SLA 2和END 3）、蛋白质分选（E类vps）和囊泡-液泡融合（MON 1和CCZ 1）的基因相互作用以处理A30 P; YPP 1还参与信息素触发的受体介导的内吞作用。我们的数据表明，YPP 1介导的运输A30 P的液泡通过内吞途径。
Using a genetic screen we discovered that YGR198w (named YPP1), which is an essential Saccharomyces cerevisiae gene of unknown function, suppresses the toxicity of an α-synuclein (α-syn) mutant (A30P) that is associated with early onset Parkinson's disease. Here, we show that YPP1 suppresses lethality of A30P, but not of wild-type α-syn or the A53T mutant. The Ypp1 protein, when overexpressed, drives each of the three α-syns into vesicles that bud off the plasma membrane, but only A30P-containing vesicles traffick to and merge with the vacuole, where A30P is proteolytically degraded. We show that Ypp1p binds to A30P but not the other two α-syns; that YPP1 interacts with genes involved in endocytosis/actin dynamics (SLA1, SLA2, and END3), protein sorting (class E vps), and vesicle-vacuole fusion (MON1 and CCZ1) to dispose of A30P; and that YPP1 also participates in pheromone-triggered receptor-mediated endocytosis. Our data reveal that YPP1 mediates the trafficking of A30P to the vacuole via the endocytic pathway.