在交配前,一个酿酒酵母细胞必须在其附近检测表达大量某种性信息素的一个伙伴细胞。这个信息素检测系统涉及MAP激酶信号传导级联,而分泌最高浓度信息素的潜在伙伴就是被选择的交配对象。
一项将实验和数学模拟相结合的研究工作表明,交配决策是一种所谓的“all-or-none”开关式响应:要使交配开始,酵母细胞周围的信息素必须达到一个临界浓度,而如果这个浓度达不到,酵母细胞将继续进行无性繁殖。这种决策的做出是很快的,在与一种信息素最初接触2分钟内就能完成。
骨架蛋白Ste5(它在一个活性复合物中结合MAPK级联成分)是信息素的作用的直接调控因子。如果相似的超灵敏机制出现在哺乳动物信号作用通道中,它们面对导致疾病的突变也许会尤为脆弱,因此可能会被证明是重要的治疗目标。(生物谷Bioon.com)
生物谷推荐原文出处:
Nature doi:10.1038/nature08946
The scaffold protein Ste5 directly controls a switch-like mating decision in yeast
Mohan K. Malleshaiah1,6, Vahid Shahrezaei3,6, Peter S. Swain4,5 & Stephen W. Michnick1,2
1 Département de Biochimie,
2 Centre Robert-Cedergren, Bio-Informatique et Génomique Université de Montréal, C.P. 6128, Succursale centre-ville Montréal, Québec H3C 3J7, Canada
3 Department of Mathematics, Imperial College London, South Kensington Campus, London SW7 2AZ, UK
4 Department of Physiology, McGill University, 3655 Promenade Sir William Osler, Montréal, Québec H3G 1Y6, Canada
5 Centre for Systems Biology at Edinburgh, University of Edinburgh, Edinburgh EH9 3JD, UK
6 These authors contributed equally to this work.
Evolution has resulted in numerous innovations that allow organisms to increase their fitness by choosing particular mating partners, including secondary sexual characteristics, behavioural patterns, chemical attractants and corresponding sensory mechanisms1. The haploid yeast Saccharomyces cerevisiae selects mating partners by interpreting the concentration gradient of pheromone secreted by potential mates through a network of mitogen-activated protein kinase (MAPK) signalling proteins2, 3. The mating decision in yeast is an all-or-none, or switch-like, response that allows cells to filter weak pheromone signals, thus avoiding inappropriate commitment to mating by responding only at or above critical concentrations when a mate is sufficiently close4. The molecular mechanisms that govern the switch-like mating decision are poorly understood. Here we show that the switching mechanism arises from competition between the MAPK Fus3 and a phosphatase Ptc1 for control of the phosphorylation state of four sites on the scaffold protein Ste5. This competition results in a switch-like dissociation of Fus3 from Ste5 that is necessary to generate the switch-like mating response. Thus, the decision to mate is made at an early stage in the pheromone pathway and occurs rapidly, perhaps to prevent the loss of the potential mate to competitors. We argue that the architecture of the Fus3–Ste5–Ptc1 circuit generates a novel ultrasensitivity mechanism, which is robust to variations in the concentrations of these proteins. This robustness helps assure that mating can occur despite stochastic or genetic variation between individuals. The role of Ste5 as a direct modulator of a cell-fate decision expands the functional repertoire of scaffold proteins beyond providing specificity and efficiency of information processing5, 6. Similar mechanisms may govern cellular decisions in higher organisms and be disrupted in cancer.