Coordination of Rho family GTPase activities to orchestrate cytoskeleton responses during cell wound repair.
Coordination of Rho family GTPase activities to orchestrate cytoskeleton responses during cell wound repair.
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DOI：
10.1016/j.cub.2013.11.048
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发表时间：
2014-01-20
期刊：
影响因子：
9.2
通讯作者：
Parkhurst, Susan M.
中科院分区：
文献类型：
--
作者：
Abreu-Blanco, Maria Teresa;Verboon, Jeffrey M.;Parkhurst, Susan M.
细胞使用复杂、有效和保守的反应来修复其质膜中的破坏，所述反应涉及膜塞的形成和肌动球蛋白环的组装。在这里，我们描述了Rho家族GTP酶如何调节细胞骨架机械在单细胞创伤修复的遗传学上顺从的果蝇胚胎模型。我们发现，Rho，Rac和Cdc 42迅速积累伤口周围，并分离成动态的，部分重叠的区域。遗传学和药理学分析表明，每个GTdR对修复过程有特定的贡献。Rho 1是肌球蛋白II激活所必需的，导致其与肌动蛋白的关联。Rho 1与Cdc 42沿着是肌动蛋白丝形成和随后的肌动球蛋白环稳定所必需的。Rac是肌动蛋白向伤口移动所必需的。这些GTP酶的贡献受到GTP酶本身和细胞骨架之间的串扰。我们发现Rho 1 GTdR同时使用几个下游效应子，包括Diaphanous，Rok和Pkn来介导其功能。我们的研究结果表明，这三个Rho GTP酶是必要的，以控制和协调肌动蛋白和肌球蛋白的动力学在果蝇胚胎的单细胞伤口修复。创伤触发Rho GTP酶阵列的形成，其充当调节细胞骨架的信号中心。反过来，Rho GTP酶本身之间以及与细胞骨架之间的协调串扰是肌动球蛋白环的组装/拆卸和易位所需的。细胞创伤修复反应是如何响应细胞的需要局部激活特定途径的一个例子。
Cells heal disruptions in their plasma membrane using a sophisticated, efficient, and conserved response involving the formation of a membrane plug and assembly of an actomyosin ring. Here we describe how Rho family GTPases modulate the cytoskeleton machinery during single cell wound repair in the genetically amenable Drosophila embryo model. We find that Rho, Rac and Cdc42 rapidly accumulate around the wound and segregate into dynamic, partially overlapping, zones. Genetic and pharmacological assays show that each GTPase makes specific contributions to the repair process. Rho1 is necessary for myosin II activation leading to its association with actin. Rho1, along with Cdc42, are necessary for actin filament formation and subsequent actomyosin ring stabilization. Rac is necessary for actin mobilization towards the wound. These GTPase contributions are subject to crosstalk among the GTPases themselves and with the cytoskeleton. We find Rho1 GTPase uses several downstream effectors, including Diaphanous, Rok, and Pkn, simultaneously to mediate its functions. Our results reveal that the three Rho GTPases are necessary to control and coordinate actin and myosin dynamics during single cell wound repair in the Drosophila embryo. Wounding triggers the formation of Rho GTPases arrays that act as signaling centers that modulate the cytoskeleton. In turn, coordinated crosstalk among the Rho GTPases themselves, as well as with the cytoskeleton, are required for assembly/disassembly and translocation of the actomyosin ring. The cell wound repair response is an example of how specific pathways can be activated locally in response to the cell’s needs.
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影响因子：
7.8
作者：
McNeil, PL;Steinhardt, RA
通讯作者：
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作者：
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