Galpha12/13 regulate epiboly by inhibiting E-cadherin activity and modulating the actin cytoskeleton.
Galpha12/13 regulate epiboly by inhibiting E-cadherin activity and modulating the actin cytoskeleton.
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DOI：
10.1083/jcb.200805148
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发表时间：
2009-03-23
期刊：
影响因子：
--
通讯作者：
Solnica-Krezel L
中科院分区：
文献类型：
--
作者：
Lin F;Chen S;Sepich DS;Panizzi JR;Clendenon SG;Marrs JA;Hamm HE;Solnica-Krezel L
在斑马鱼原肠胚形成过程中，Epiboly 使卵黄细胞上的胚盘扩散并变薄，并涉及多个细胞层的协调运动。尽管最近的研究已经开始阐明这些表观运动背后的过程，但所涉及的细胞和分子机制仍有待完全确定。在这里，我们发现，Gα12/13 信号传导改变的原肠胚表现出深层细胞的表代谢运动延迟、背侧先行细胞的异常运动以及细胞与胚盘的解离，表型 e-钙粘蛋白突变体。生化和遗传学研究表明，Gα12/13 部分通过与 E-钙粘蛋白的细胞质末端结合来调节表观代谢，从而抑制 E-钙粘蛋白活性和细胞粘附。此外，我们证明 Gα12/13 通过 RhoGEF/Rho 依赖性途径调节肌动蛋白细胞骨架组织，从而调节包膜层的表观代谢运动。这些结果提供了第一个体内证据，证明 Gα12/13 通过两种不同的机制调节外泌体：限制 E-钙粘蛋白活性和调节肌动蛋白细胞骨架的组织。
Epiboly spreads and thins the blastoderm over the yolk cell during zebrafish gastrulation, and involves coordinated movements of several cell layers. Although recent studies have begun to elucidate the processes that underlie these epibolic movements, the cellular and molecular mechanisms involved remain to be fully defined. Here, we show that gastrulae with altered Gα12/13 signaling display delayed epibolic movement of the deep cells, abnormal movement of dorsal forerunner cells, and dissociation of cells from the blastoderm, phenocopying e-cadherin mutants. Biochemical and genetic studies indicate that Gα12/13 regulate epiboly, in part by associating with the cytoplasmic terminus of E-cadherin, and thereby inhibiting E-cadherin activity and cell adhesion. Furthermore, we demonstrate that Gα12/13 modulate epibolic movements of the enveloping layer by regulating actin cytoskeleton organization through a RhoGEF/Rho-dependent pathway. These results provide the first in vivo evidence that Gα12/13 regulate epiboly through two distinct mechanisms: limiting E-cadherin activity and modulating the organization of the actin cytoskeleton.
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