RhoA GTPase inhibition organizes contraction during epithelial morphogenesis.
RhoA GTPase inhibition organizes contraction during epithelial morphogenesis.
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DOI：
10.1083/jcb.201603077
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发表时间：
2016-08-29
期刊：
影响因子：
--
通讯作者：
Martin AC
中科院分区：
文献类型：
--
作者：
Mason FM;Xie S;Vasquez CG;Tworoger M;Martin AC
Mason等人表明，RhoA活性在空间和时间上受到GEF/GAP模块的调节，该模块调节细胞行为，是果蝇形态发生过程中适当的组织折叠和形状所必需的。在形态发生过程中，单个细胞内肌动球蛋白细胞骨架的收缩驱动细胞形状变化，从而折叠组织。细胞骨架收缩性的协调是通过调节RhoA GTPase活性介导的。鸟嘌呤核苷酸交换因子（GEFs）激活和gtpase激活蛋白（gap）抑制RhoA活性。大多数关于组织折叠的研究，包括顶端收缩，都集中在GEFs如何激活RhoA以促进细胞收缩，而很少研究GAPs如何发挥重要作用。在这里，我们确定了RhoA GAP， Cumberland GAP (C-GAP)，它与RhoA GEF， RhoGEF2协调，在果蝇顶端收缩过程中组织时空收缩的关键作用。C-GAP在空间上将RhoA通路的活性限制在顶端皮层的中心位置。RhoGEF2脉冲先于肌球蛋白，而C-GAP是搏动所必需的，这表明收缩脉冲是由RhoA活性循环引起的。最后，C-GAP表达水平影响细胞形态从可逆到不可逆的转变，从而定义组织形态改变的开始。我们的数据表明，RhoA活性循环和调节RhoGEF2与C-GAP的比例是组织折叠所必需的。
Mason et al. show that RhoA activity is regulated in space and time by a GEF/GAP module that tunes cell behavior and is required for proper tissue folding and shape during Drosophila morphogenesis. During morphogenesis, contraction of the actomyosin cytoskeleton within individual cells drives cell shape changes that fold tissues. Coordination of cytoskeletal contractility is mediated by regulating RhoA GTPase activity. Guanine nucleotide exchange factors (GEFs) activate and GTPase-activating proteins (GAPs) inhibit RhoA activity. Most studies of tissue folding, including apical constriction, have focused on how RhoA is activated by GEFs to promote cell contractility, with little investigation as to how GAPs may be important. Here, we identify a critical role for a RhoA GAP, Cumberland GAP (C-GAP), which coordinates with a RhoA GEF, RhoGEF2, to organize spatiotemporal contractility during Drosophila melanogaster apical constriction. C-GAP spatially restricts RhoA pathway activity to a central position in the apical cortex. RhoGEF2 pulses precede myosin, and C-GAP is required for pulsation, suggesting that contractile pulses result from RhoA activity cycling. Finally, C-GAP expression level influences the transition from reversible to irreversible cell shape change, which defines the onset of tissue shape change. Our data demonstrate that RhoA activity cycling and modulating the ratio of RhoGEF2 to C-GAP are required for tissue folding.
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影响因子：
3.3
作者：
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