Inhibition of Ras activity coordinates cell fusion with cell-cell contact during yeast mating.
Inhibition of Ras activity coordinates cell fusion with cell-cell contact during yeast mating.
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DOI：
10.1083/jcb.201708195
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发表时间：
2018-04-02
期刊：
影响因子：
--
通讯作者：
Martin SG
中科院分区：
文献类型：
--
作者：
Merlini L;Khalili B;Dudin O;Michon L;Vincenzetti V;Martin SG
酵母细胞壁在有性繁殖过程中被消化以允许细胞融合。细胞如何协调这一过程与细胞-细胞接触，以防止溶解是不清楚的。Merlini等人表明，Ras GAP蛋白Gap 1被募集到Ras-GTP的位点，限制Ras活性并保护细胞免于由于过早融合尝试而导致的裂解。在裂殖酵母裂殖酵母中，信息素信号传导参与由G蛋白偶联受体Ras和丝裂原活化蛋白激酶（MAPK）级联组成的信号传导途径，所述丝裂原活化蛋白激酶级联触发性分化和配子融合。细胞-细胞融合需要局部细胞壁消化，这依赖于最初动态的肌动蛋白融合焦点，其在结构上的信号级联的局部富集后变得稳定。我们构建了活性Ras 1（Ras 1-鸟苷三磷酸[GTP]）的活报告基因，其显示融合前融合结构上极性位点的Ras活性达到峰值。值得注意的是，组成型Ras 1激活促进融合焦点稳定和融合尝试，而不管细胞配对，导致细胞裂解。Ras 1的活性受到鸟苷三磷酸酶激活蛋白Gap 1的限制，Gap 1本身被募集到Ras 1-GTP的位点，并且对于阻止不合时宜的融合尝试至关重要。我们认为Ras活性的负反馈控制抑制了MAPK信号，并将融合与细胞-细胞接合结合起来。
The yeast cell wall is digested to allow cell fusion during sexual reproduction. How cells coordinate this process with cell–cell contact to prevent lysis is unclear. Merlini et al. show that the Ras GAP protein Gap1, which is recruited to sites of Ras-GTP, restricts Ras activity and protects cells from lysis due to premature fusion attempts. In the fission yeast Schizosaccharomyces pombe, pheromone signaling engages a signaling pathway composed of a G protein–coupled receptor, Ras, and a mitogen-activated protein kinase (MAPK) cascade that triggers sexual differentiation and gamete fusion. Cell–cell fusion requires local cell wall digestion, which relies on an initially dynamic actin fusion focus that becomes stabilized upon local enrichment of the signaling cascade on the structure. We constructed a live-reporter of active Ras1 (Ras1–guanosine triphosphate [GTP]) that shows Ras activity at polarity sites peaking on the fusion structure before fusion. Remarkably, constitutive Ras1 activation promoted fusion focus stabilization and fusion attempts irrespective of cell pairing, leading to cell lysis. Ras1 activity was restricted by the guanosine triphosphatase–activating protein Gap1, which was itself recruited to sites of Ras1-GTP and was essential to block untimely fusion attempts. We propose that negative feedback control of Ras activity restrains the MAPK signal and couples fusion with cell–cell engagement.
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