在交配前,一個(gè)釀酒酵母細(xì)胞必須在其附近檢測表達(dá)大量某種性信息素的一個(gè)伙伴細(xì)胞,。這個(gè)信息素檢測系統(tǒng)涉及MAP激酶信號傳導(dǎo)級聯(lián),,而分泌最高濃度信息素的潛在伙伴就是被選擇的交配對象。
一項(xiàng)將實(shí)驗(yàn)和數(shù)學(xué)模擬相結(jié)合的研究工作表明,,交配決策是一種所謂的“all-or-none”開關(guān)式響應(yīng):要使交配開始,,酵母細(xì)胞周圍的信息素必須達(dá)到一個(gè)臨界濃度,而如果這個(gè)濃度達(dá)不到,,酵母細(xì)胞將繼續(xù)進(jìn)行無性繁殖,。這種決策的做出是很快的,在與一種信息素最初接觸2分鐘內(nèi)就能完成,。
骨架蛋白Ste5(它在一個(gè)活性復(fù)合物中結(jié)合MAPK級聯(lián)成分)是信息素的作用的直接調(diào)控因子,。如果相似的超靈敏機(jī)制出現(xiàn)在哺乳動物信號作用通道中,它們面對導(dǎo)致疾病的突變也許會尤為脆弱,,因此可能會被證明是重要的治療目標(biāo),。(生物谷Bioon.com)
生物谷推薦原文出處:
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.