Mating yeast cells use an intrinsic polarity site to assemble a pheromone-gradient tracking machine

Mating yeast cells use an intrinsic polarity site to assemble a pheromone-gradient tracking machine
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交配酵母细胞使用固有极性位点来组装信息素梯度跟踪机

DOI:
10.1083/jcb.201901155
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发表时间:
2019
影响因子:
7.8
通讯作者:
Stone, David E.
Stone, David E.
中科院分区:
生物学1区
文献类型:
--
作者:
Wang, Xin;Tian, Wei;Banh, Bryan T.;Statler, Bethanie-Michelle;Liang, Jie;Stone, David E.

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发芽酵母的交配依赖于趋化性,这是一个基本的细胞过程。这两种交配类型的酵母分泌肽信息素,这些信息素与相反类型的细胞上的GPCRs结合。细胞通过确定信息素来源的方向并极化它们向信息素来源的生长来寻找和联系伴侣。肌动蛋白直接分泌到趋化生长部位(CS)产生交配突起。当信息素刺激的细胞无法感觉到梯度时,它们就会在下一个细胞周期中发芽的地方形成交配投影,这个位置被称为默认极性位置(DS)。已经提出了许多模型来解释酵母梯度感应,但没有一个模型解决了细胞如何可靠地从内在决定的DS切换到梯度排列的CS,尽管空间信号很弱。在这里,我们证明,在交配细胞中,最初统一的受体和G蛋白首先极化到DS,然后沿着质膜重新分布,直到它们到达CS。我们的数据表明,在我们所称的梯度跟踪机(GTM)的组装过程中,信号、极性和运输蛋白定位于DS。受体的不同激活触发反馈机制,使胞吐作用向上,内吞作用向下倾斜,从而使GTM重新分配到信息素来源。当受体的峰值集中在CS,内吞机制围绕在它周围时,GTM稳定。一个计算模型模拟了GTM的跟踪和稳定,并正确地预测了它在单个地点的组装有助于交配保真度。
The mating of budding yeast depends on chemotropism, a fundamental cellular process. The two yeast mating types secrete peptide pheromones that bind to GPCRs on cells of the opposite type. Cells find and contact a partner by determining the direction of the pheromone source and polarizing their growth toward it. Actin-directed secretion to the chemotropic growth site (CS) generates a mating projection. When pheromone-stimulated cells are unable to sense a gradient, they form mating projections where they would have budded in the next cell cycle, at a position called the default polarity site (DS). Numerous models have been proposed to explain yeast gradient sensing, but none address how cells reliably switch from the intrinsically determined DS to the gradient-aligned CS, despite a weak spatial signal. Here we demonstrate that, in mating cells, the initially uniform receptor and G protein first polarize to the DS, then redistribute along the plasma membrane until they reach the CS. Our data indicate that signaling, polarity, and trafficking proteins localize to the DS during assembly of what we call the gradient tracking machine (GTM). Differential activation of the receptor triggers feedback mechanisms that bias exocytosis upgradient and endocytosis downgradient, thus enabling redistribution of the GTM toward the pheromone source. The GTM stabilizes when the receptor peak centers at the CS and the endocytic machinery surrounds it. A computational model simulates GTM tracking and stabilization and correctly predicts that its assembly at a single site contributes to mating fidelity.
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