Zds1/Zds2-PP2ACdc55 complex specifies signaling output from Rho1 GTPase.
Zds1/Zds2-PP2ACdc55 complex specifies signaling output from Rho1 GTPase.
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DOI：
10.1083/jcb.201508119
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发表时间：
2016-01-04
期刊：
影响因子：
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通讯作者：
Yoshida S
中科院分区：
文献类型：
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作者：
Jonasson EM;Rossio V;Hatakeyama R;Abe M;Ohya Y;Yoshida S
Zds1/Zds2-PP2ACdc55与Rho1 GTP酶形成一个复合体，通过调节发芽酵母中的Rho1间隙来指定Rho1信号转导结果。发芽酵母Rho1鸟苷三磷酸酶(GTPase)通过调节细胞壁葡聚糖的合成和肌动蛋白的组织，在极化细胞的生长中起着至关重要的作用。在细胞壁损伤时，Rho1通过激活细胞壁完整性(CWI)Pkc1-丝裂原活化蛋白激酶(MAPK)通路来阻止极化的细胞生长并修复伤口。一个基本的问题是，活性Rho1如何在不同的条件下促进不同的信号输出。在这里，我们发现Zds1/Zds2蛋白磷酸酶2ACdc55(PP2ACdc55)复合体是一种新的Rho1效应因子，调节Rho1信号的特异性。ZDS1/ZDS2-PP2ACdc55通过抑制Rho1 GTP酶激活蛋白(GAP)LRG1促进极化生长和细胞壁合成，但通过稳定另一个Rho1 GAP Sac7抑制CWI途径，表明活性Rho1在应激反应中偏向于细胞生长。相反，在细胞壁损伤时，Pkc1-Mpk1活性抑制皮质PP2ACdc55，确保Rho1优先激活CWI途径进行细胞壁修复。我们认为，PP2ACdc55规定了Rho1信号输出，Rho1-PP2ACdc55和Rho1-Pkc1之间的相互拮抗解释了为什么一次只有一条信号通路被激活。
Zds1/Zds2–PP2ACdc55 forms a complex with Rho1 GTPase and specifies Rho1 signaling outcome by regulating Rho1 GAPs in budding yeast. Budding yeast Rho1 guanosine triphosphatase (GTPase) plays an essential role in polarized cell growth by regulating cell wall glucan synthesis and actin organization. Upon cell wall damage, Rho1 blocks polarized cell growth and repairs the wounds by activating the cell wall integrity (CWI) Pkc1–mitogen-activated protein kinase (MAPK) pathway. A fundamental question is how active Rho1 promotes distinct signaling outputs under different conditions. Here we identified the Zds1/Zds2–protein phosphatase 2ACdc55 (PP2ACdc55) complex as a novel Rho1 effector that regulates Rho1 signaling specificity. Zds1/Zds2–PP2ACdc55 promotes polarized growth and cell wall synthesis by inhibiting Rho1 GTPase-activating protein (GAP) Lrg1 but inhibits CWI pathway by stabilizing another Rho1 GAP, Sac7, suggesting that active Rho1 is biased toward cell growth over stress response. Conversely, upon cell wall damage, Pkc1–Mpk1 activity inhibits cortical PP2ACdc55, ensuring that Rho1 preferentially activates the CWI pathway for cell wall repair. We propose that PP2ACdc55 specifies Rho1 signaling output and that reciprocal antagonism between Rho1–PP2ACdc55 and Rho1–Pkc1 explains how only one signaling pathway is robustly activated at a time.