Cdc42p, GTP Hydrolysis and the Cell’s Sense of Direction
Cdc42p, GTP Hydrolysis and the Cell’s Sense of Direction
复制标题
Cdc42p、GTP 水解和细胞的方向感
作者：
Javier E Irazoqui;A. Gladfelter;D. Lew
GTdcdc 42 p对于动物和真菌中极性的建立是必不可少的。1人Cdc 42 p可以在功能上取代酵母Cdc 42 p，2表明高度的进化保守性。目前的Cdc 42 p作用模型一般遵循Ras的信号传导模式，其中受体对起始刺激的响应导致鸟嘌呤核苷酸交换因子（GEF）触发Ras的GTP负载，从而导致下游效应物的参与和随后的细胞增殖。Ras范式的关键支持来自以下发现：Ras的致癌形式不能水解GTP，因此与GTP组成性结合，即使在没有刺激的情况下，也能模拟上游受体的组成性信号传导的作用。尝试评估这种范式是否对Cdc 42 p诱导的酵母细胞极化有效，产生了相互矛盾的结果。3 -6在这里，我们讨论了关于这个问题的可用信息，并得出结论，与Ras信号传导不同，Cdc 42 p指导的极性建立还需要GTP和GDP结合形式之间的循环。我们认为，这种循环是一个很少研究的Cdc 42 p的“功能”的关键：它的能力，指定一个独特的部分细胞皮层成为极化网站，并成为集中在该网站。
The GTPase Cdc42p is essential for polarity establishment in animals and fungi.1 Human Cdc42p can functionally replace yeast Cdc42p,2 indicating a high degree of evolutionary conservation. Current models of Cdc42p action generally follow the signaling paradigm established for Ras, in which receptors responding to an initiating stimulus cause guanine nucleotide exchange factors (GEFs) to trigger GTP-loading of Ras, leading to engagement of downstream effectors and ensuing cell proliferation. Key support for the Ras paradigm came from the finding that oncogenic forms of Ras, unable to hydrolyze GTP and therefore constitutively GTP-bound, mimicked the effect of constitutive signaling by the upstream receptors even in the absence of stimuli. Attempts to assess whether or not this paradigm is valid for Cdc42p-induced polarization of yeast cells have yielded conflicting results.3-6 Here, we discuss the available information on this issue and conclude that unlike Ras signaling, Cdc42p directed polarity establishment additionally requires cycling between GTP- and GDP-bound forms. We suggest that such cycling is critical for a little-studied “function” of Cdc42p: its ability to designate a unique portion of the cell cortex to become the polarization site, and to become concentrated at that site.