Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling.
Single-cell profiling screen identifies microtubule-dependent reduction of variability in signaling.
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DOI：
10.15252/msb.20167390
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发表时间：
2018-04-04
影响因子：
9.9
通讯作者：
Brent R
中科院分区：
文献类型：
--
作者：
Pesce CG;Zdraljevic S;Peria WJ;Bush A;Repetto MV;Rockwell D;Yu RC;Colman-Lerner A;Brent R
尽管蛋白质丰度和细胞状态存在差异，但同基因细胞群通常对信号做出一致的反应。此前，我们发现了酿酒酵母信息素响应系统（PRS）中减少细胞间信号强度和细胞响应变异性的过程。在这里，我们筛选了 1,141 个非必需基因，鉴定出 50 个“变异基因”。大多数对 PRS 的强度和变异性具有独特的、可分离的影响，将这些量定义为系统行为的遗传上不同的“轴”。三个基因影响细胞质微管功能：BIM1、GIM2 和 GIM4。我们使用遗传和化学扰动表明，如果没有微管，PRS 输出会减少，但变异性不受影响，而当微管存在但其功能受到干扰时，输出有时会降低，但其变异性始终很高。由微管扰动引起的变异性增加需要 PRS MAP 激酶 Fus3 以及 Ste5 处或上游的过程，Ste5 是 Fus3 必须结合才能激活的膜定位支架。 Ste5 定位动态的可视化表明，微管的扰动会破坏膜信号位点上 Ste5 的稳定性。这种微管扰动导致哺乳动物异常的命运和极性决定这一事实表明，微管依赖性信号稳定也可能在整个后生动物中发挥作用。
Populations of isogenic cells often respond coherently to signals, despite differences in protein abundance and cell state. Previously, we uncovered processes in the Saccharomyces cerevisiae pheromone response system (PRS) that reduced cell‐to‐cell variability in signal strength and cellular response. Here, we screened 1,141 non‐essential genes to identify 50 “variability genes”. Most had distinct, separable effects on strength and variability of the PRS, defining these quantities as genetically distinct “axes” of system behavior. Three genes affected cytoplasmic microtubule function: BIM1, GIM2, and GIM4. We used genetic and chemical perturbations to show that, without microtubules, PRS output is reduced but variability is unaffected, while, when microtubules are present but their function is perturbed, output is sometimes lowered, but its variability is always high. The increased variability caused by microtubule perturbations required the PRS MAP kinase Fus3 and a process at or upstream of Ste5, the membrane‐localized scaffold to which Fus3 must bind to be activated. Visualization of Ste5 localization dynamics demonstrated that perturbing microtubules destabilized Ste5 at the membrane signaling site. The fact that such microtubule perturbations cause aberrant fate and polarity decisions in mammals suggests that microtubule‐dependent signal stabilization might also operate throughout metazoans.
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影响因子：
64.5
作者：
Colman-Lerner, A;Chin, TE;Brent, R
通讯作者：
Brent, R
影响因子：
48
作者：
Gordon, Andrew;Colman-Lerner, Alejandro;Brent, Roger
通讯作者：
Brent, Roger
影响因子：
7.8
作者：
Cavalli, V;Kujala, P;Goldstein, LSB
通讯作者：
Goldstein, LSB
影响因子：
9.9
作者：
Bush A;Vasen G;Constantinou A;Dunayevich P;Patop IL;Blaustein M;Colman-Lerner A
通讯作者：
Colman-Lerner A
DOI：
10.1083/jcb.201111123
发表时间：
2012-04-02
期刊：
The Journal of cell biology
影响因子：
--
作者：
Erlemann S;Neuner A;Gombos L;Gibeaux R;Antony C;Schiebel E
通讯作者：
Schiebel E