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45 years of cGMP research in Dictyostelium: Understanding the regulation and function of the cGMP pathway for cell movement and chemotaxis
Molecular Biology of the Cell ( IF 3.1 ) Pub Date : 2021-08-04 , DOI: 10.1091/mbc.e21-04-0171
Peter J M van Haastert 1 , Ineke Keizer-Gunnink 1 , Henderikus Pots 1 , Claudia Ortiz-Mateos 1 , Douwe Veltman 1 , Wouter van Egmond 1 , Arjan Kortholt 1
Affiliation  

In Dictyostelium chemoattractants induce a fast cGMP response that mediates myosin filament formation in the rear of the cell. The major cGMP signaling pathway consists of a soluble guanylyl cyclase sGC, a cGMP-stimulated cGMP-specific phosphodiesterase and the cGMP-target protein GbpC. Here we combine published experiments with many unpublished experiments performed in the past 45 years on the regulation and function of the cGMP signaling pathway. The chemoattractants stimulate heterotrimeric Gαβγ and monomeric Ras proteins. A fraction of the soluble guanylyl cyclase sGC binds with high affinity to a limited number of membrane binding site, which is essential for sGC to become activated by Ras and Gα proteins. sGC can also bind to F-actin; binding to branched F-actin in pseudopods enhances basal sGC activity, whereas binding to parallel F-actin in the cortex reduces sGC activity. The cGMP pathway mediates cell polarity by inhibiting the rear: in unstimulated cells by sGC activity in the branched F-actin of pseudopods, in a shallow gradient by stimulated cGMP formation in pseudopods at the leading edge, and during cAMP oscillation to erase the previous polarity and establish a new polarity axis that aligns with the direction of the passing cAMP wave.



中文翻译:

45 年的网柄菌 cGMP 研究:了解 cGMP 通路对细胞运动和趋化性的调节和功能

网柄菌属中趋化剂诱导快速的 cGMP 反应,介导细胞后部肌球蛋白丝的形成。主要的 cGMP 信号通路由可溶性鸟苷酸环化酶 sGC、cGMP 刺激的 cGMP 特异性磷酸二酯酶和 cGMP 靶蛋白 GbpC 组成。在这里,我们将已发表的实验与过去 45 年来针对 cGMP 信号通路的调节和功能进行的许多未发表的实验相结合。化学引诱剂刺激异三聚体 Gαβγ 和单体 Ras 蛋白。一部分可溶性鸟苷酸环化酶 sGC 以高亲和力与有限数量的膜结合位点结合,这对于 sGC 被 Ras 和 Gα 蛋白激活是必不可少的。sGC 也可以与 F-actin 结合;与伪足中的分支 F-肌动蛋白结合增强了基础 sGC 活性,而与皮质中的平行 F-肌动蛋白结合会降低 sGC 活性。cGMP 通路通过抑制后部来介导细胞极性:在未刺激的细胞中,通过伪足的分支 F-肌动蛋白中的 sGC 活性,在浅梯度中通过在前缘的伪足中刺激 cGMP 形成,以及在 cAMP 振荡期间消除先前的极性并建立一个与通过的 cAMP 波方向对齐的新极性轴。

更新日期:2021-08-05
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