Modular activation of Rho1 by GPCR signalling imparts polarized myosin II activation during morphogenesis
Modular activation of Rho1 by GPCR signalling imparts polarized myosin II activation during morphogenesis
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DOI：
10.1038/ncb3302
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发表时间：
2016-03-01
影响因子：
21.3
通讯作者：
Lecuit, Thomas
中科院分区：
文献类型：
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作者：
Kerridge, Stephen;Munjal, Akankshi;Lecuit, Thomas
在组织形态发生过程中，细胞形态的极化变化是通过控制肌球蛋白II的亚细胞分布而产生的。例如，在果蝇原肠形成过程中，顶端收缩和细胞嵌入是由顶端内侧肌凝蛋白II脉冲介导的，肌凝蛋白II的极化积累稳定了这些变形。目前尚不清楚组织特异性因子如何控制不同模式的肌球蛋白II激活和棘轮样肌球蛋白II动力学。在这里，我们报道了一条由异三聚体G蛋白G α(12/13)、G β 13F和G γ 1组成的共同途径在果蝇原肠形成过程中激活和极化肌球蛋白II的功能。G α(12/13)和G β 13F/ γ 1复合体构成不同的信号传导模块，以组织依赖的方式调节肌球蛋白II的中尖和/或连接动态。我们鉴定了一种称为Smog的无所不在表达的GPCR，这是细胞嵌入和根尖收缩所必需的。Smog与其他gpcr一起定量控制G蛋白，导致肌球蛋白II的逐步激活和不可逆的细胞形状变化。我们认为GPCR和G蛋白构成了控制上皮细胞肌动球蛋白收缩性的一般途径，并且该途径的活性受到组织特异性调节因子的极化。
Polarized cell shape changes during tissue morphogenesis arise by controlling the subcellular distribution of myosin II. For instance, during Drosophila melanogaster gastrulation, apical constriction and cell intercalation are mediated by medial-apical myosin II pulses that power deformations, and polarized accumulation of myosin II that stabilizes these deformations. It remains unclear how tissue-specific factors control different patterns of myosin II activation and the ratchet-like myosin II dynamics. Here we report the function of a common pathway comprising the heterotrimeric G proteins G alpha(12/13), G beta 13F and G gamma 1 in activating and polarizing myosin II during Drosophila gastrulation. G alpha(12/13) and the G beta 13F/gamma 1 complex constitute distinct signalling modules, which regulate myosin II dynamics medial-apically and/or junctionally in a tissue-dependent manner. We identify a ubiquitously expressed GPCR called Smog required for cell intercalation and apical constriction. Smog functions with other GPCRs to quantitatively control G proteins, resulting in stepwise activation of myosin II and irreversible cell shape changes. We propose that GPCR and G proteins constitute a general pathway for controlling actomyosin contractility in epithelia and that the activity of this pathway is polarized by tissue-specific regulators.