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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A Rab GAP cascade defines the boundary between two Rab GTPases on the secretory pathway
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A Rab GAP cascade defines the boundary between two Rab GTPases on the secretory pathway

机译：Rab GAP级联定义了分泌途径上两个Rab GTPases之间的边界

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摘要

Membrane traffic along the endocytic and exocytic pathways relies on the appropriate localization and activation of a series of different Rab GTPases. Rabs are activated by specific guanine nucleotide exchange factors (GEFs) and inactivated by GTPase-activating proteins (GAPs). GEF cascades, in which one Rab in its GTP-bound form recruits the GEF that activates the next Rab along the pathway, can account for the sequential activation of a series of Rabs, but it does not explain how the first Rab is inactivated after the next Rab has been activated. We present evidence for a counter-current GAP cascade that serves to restrict the spatial and temporal overlap of 2 Rabs, Ypt1p and Ypt32p, on the exocytic pathway in Saccharomyces cerevisiae. We show that Gyp1p, a GAP for Yptip, specifically interacts with Ypt32p, and that this interaction is important for the localization and stability of Gypip. Moreover, we demonstrate that, in WT cells, Ypt1p compartments are converted over time into Ypt32p compartments, whereas in gyp 1△ cells there is a significant increase in compartments containing both proteins that reflects a slower transition from Yptip to Ypt32p. GEF cascades working in concert with counter-current GAP cascades could generate a programmed series of Rab conversions responsible for regulating the choreography of membrane traffic.
机译：沿内吞和胞外途径的膜运输依赖于一系列不同的Rab GTPases的适当定位和激活。 Rabs被特定的鸟嘌呤核苷酸交换因子（GEFs）激活，并被GTPase激活蛋白（GAPs）灭活。 GEF级联，其中一个GTP结合形式的Rab募集了可激活该途径的下一个Rab的GEF，可以解释一系列Rabs的顺序激活，但是并不能解释第一个Rab在激活后如何被灭活。下一个Rab已被激活。我们提供了逆流GAP级联的证据，该级联用于限制酿酒酵母胞外途径上的两个Rabs Ypt1p和Ypt32p的时空重叠。我们表明，Gyp1p，Yptip的GAP，特别是与Ypt32p相互作用，并且这种相互作用对于Gypip的定位和稳定性很重要。此外，我们证明，在WT细胞中，Ypt1p间隔随时间转换为Ypt32p间隔，而在gyp 1△细胞中，包含这两种蛋白质的间隔明显增加，这反映了从Yptip到Ypt32p的缓慢转变。与逆流GAP级联协同工作的GEF级联可以产生一系列编程的Rab转化，负责调节膜运输的编排。

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