Simon M N, De Virgilio C, Souza B, Pringle J R, Abo A, Reed S I
Scripps Research Institute, Department of Molecular Biology, La Jolla, California 92037, USA.
Nature. 1995 Aug 24;376(6542):702-5. doi: 10.1038/376702a0.
In the budding yeast Saccharomyces cerevisiae, the process of conjugation of haploid cells of genotype MATa and MAT alpha to form MATa/alpha diploids is triggered by pheromones produced by each mating type. These pheromones stimulate a cellular response by interaction with receptors linked to a heterotrimeric G protein. Although genetic analysis indicates that the pheromone signal is transmitted through the G beta gamma dimer, the initial target(s) of G protein activation remain to be determined. Temperature-sensitive cells with mutations of the CDC24 and CDC42 genes, which are incapable of budding and of generating cell polarity at the restrictive temperature, are also unable to mate. Cdc24 acts as a guanylyl-nucleotide-exchange factor for the Rho-type GTPase Cdc42, which has been shown to be a fundamental component of the molecular machinery controlling morphogenesis in eukaryotic cells. Therefore, the inability of cdc24 and cdc42 mutants to mate has been presumed to be due to a requirement for generation of cell polarity and related morphogenetic events during conjugation. But here we show that Cdc42 has a direct signalling role in the mating-pheromone response between the G protein and the downstream protein kinase cascade.
在出芽酵母酿酒酵母中，基因型为MATa和MATα的单倍体细胞结合形成MATa/α二倍体的过程由每种交配型产生的信息素触发。这些信息素通过与连接到异源三聚体G蛋白的受体相互作用来刺激细胞反应。虽然遗传分析表明信息素信号通过Gβγ二聚体传递，但G蛋白激活的初始靶点仍有待确定。携带CDC24和CDC42基因突变的温度敏感细胞在限制温度下无法出芽并产生细胞极性，也无法进行交配。Cdc24作为Rho型GTP酶Cdc42的鸟苷酸交换因子，已被证明是控制真核细胞形态发生的分子机制的基本组成部分。因此，推测cdc24和cdc42突变体无法交配是由于在结合过程中需要产生细胞极性和相关的形态发生事件。但我们在此表明，Cdc42在G蛋白和下游蛋白激酶级联之间的交配信息素反应中具有直接的信号传导作用。
