A GTP-exchange factor required for cell orientation
A GTP-exchange factor required for cell orientation
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DOI：
10.1038/34458
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发表时间：
1998-01-08
期刊：
影响因子：
64.8
通讯作者：
Arkowitz, RA
中科院分区：
文献类型：
--
作者：
Nern, A;Arkowitz, RA
gtpase的rho家族及其调控因子对于响应细胞外信号的细胞骨架重组和转录激活至关重要（1,2）。人们对这些分子与膜受体之间的联系知之甚少。在出芽酵母Saccharomyces cerevisiae中，单倍体细胞通过G蛋白偶联受体和G蛋白的β - γ亚基对交配信息素做出反应(3)，导致细胞周期停滞，转录激活，并向交配伴侣极化生长（4,5）。rho家族GTPase Cdc42及其交换因子Cdc24参与了交配过程（6,7），但它们的具体作用尚不清楚。在这里，我们报道了cdc24等位基因的鉴定，这些等位基因不影响营养生长，但会大大降低酵母细胞的交配能力，当暴露于交配信息素时，这些突变体会阻止生长，激活转录，并经历特征形态和肌动蛋白-细胞骨架极化，然而，突变体无法定向到信息素梯度，而是将其交配投影定位在之前的芽位附近。这些突变体在Cdc24与G蛋白β - γ亚基的结合上存在特异性缺陷。我们的研究结果表明，交换因子与异三聚体G蛋白β - γ亚基的结合将受体介导的激活与定向细胞生长联系起来。
The Rho-family of GTPases and their regulators are essential for cytoskeletal reorganization and transcriptional activation in response to extracellular signals(1,2). Little is known about what Links these molecules to membrane receptors. In the budding yeast Saccharomyces cerevisiae, haploid cells respond to mating pheromone through a G-protein-coupled receptor and the beta gamma subunit of the G protein(3), resulting in arrest of the cell cycle, transcriptional activation, and polarized growth towards a mating partner(4,5). The Rho-family GTPase Cdc42 and its exchange factor Cdc24 have been implicated in the mating process(6,7), but their specific role is unknown. Here we report the identification of cdc24 alleles that do not affect vegetative growth but drastically reduce the ability of yeast cells to mate, When exposed to mating pheromone, these mutants arrest growth, activate transcription, and undergo characteristic morphological and actin-cytoskeleton polarization, However, the mutants are unable to orient towards a pheromone gradient, and instead position their mating projection adjacent to their previous bud site. The mutants are specifically defective in the binding of Cdc24 to the G-protein beta gamma subunit, Our results demonstrate that the association of an exchange factor and the beta gamma subunit of a hetero-trimeric G protein links receptor-mediated activation to oriented cell growth.