A Gαq-Ca²⁺ signaling pathway promotes actin-mediated epidermal wound closure in C. elegans.
A Gαq-Ca²⁺ signaling pathway promotes actin-mediated epidermal wound closure in C. elegans.
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GαQ-CA²⁺信号通路促进了秀丽隐杆线虫中肌动蛋白介导的表皮伤口闭合。
DOI：
10.1016/j.cub.2011.10.050
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发表时间：
2011-12-06
期刊：
影响因子：
9.2
通讯作者：
Chisholm, Andrew D.
中科院分区：
文献类型：
--
作者：
Xu, Suhong;Chisholm, Andrew D.
皮肤创伤的修复对于动物在恶劣环境中生存是必不可少的，然而启动体内创伤修复的信号通路仍然知之甚少。In C.在线虫中，p38 MAPK级联促进对创伤的先天免疫应答，但对于创伤愈合的其他方面不是必需的。因此，我们着手确定C.秀丽隐翅虫表皮我们在这里表明，伤害成年C。线虫皮肤触发表皮Ca 2+的快速和持续上升，这对创伤后的生存至关重要。伤口引发的Ca 2+升高需要表皮TRPM通道GTL-2和IP 3R刺激的内部储存释放。我们确定了一个表皮信号转导途径，包括Gαq EGL-30和其效应PLCβ EGL-8。该途径功能的丧失损害了创伤后的存活。Gα q-Ca 2+通路不是已知的对创伤的先天免疫应答所必需的，而是促进肌动蛋白依赖性伤口闭合。伤口闭合需要Cdc 42小GT3和Arp 2/3依赖的肌动蛋白聚合，并且由Rho和非肌肉肌球蛋白负调控。最后，我们表明，死亡相关的蛋白激酶DAPK-1作为一个负调节伤口闭合。C.皮肤损伤线虫引发Ca 2+依赖性信号级联反应，促进伤口闭合，与对损伤的先天免疫反应平行。伤口闭合需要肌动蛋白聚合，并受到非肌肉肌球蛋白的负调控。
Repair of skin wounds is essential for animals to survive in a harsh environment, yet the signaling pathways initiating wound repair in vivo remain little understood. In C. elegans a p38 MAPK cascade promotes innate immune responses to wounding, but is not required for other aspects of wound healing. We therefore set out to identify additional wound response pathways in C. elegans epidermis. We show here that wounding the adult C. elegans skin triggers a rapid and sustained rise in epidermal Ca2+ that is critical for survival after wounding. The wound-triggered rise in Ca2+ requires the epidermal TRPM channel GTL-2 and IP3R-stimulated release from internal stores. We identify an epidermal signal transduction pathway that includes the Gαq EGL-30 and its effector PLCβ EGL-8. Loss of function in this pathway impairs survival after wounding. The Gαq-Ca2+ pathway is not required for known innate immune responses to wounding but instead promotes actin-dependent wound closure. Wound closure requires the Cdc42 small GTPase and Arp2/3 dependent actin polymerization, and is negatively regulated by Rho and non-muscle myosin. Finally, we show that the death-associated protein kinase DAPK-1 acts as a negative regulator of wound closure. Skin wounding in C. elegans triggers a Ca2+-dependent signaling cascade that promotes wound closure, in parallel to the innate immune response to damage. Wound closure requires actin polymerization and is negatively regulated by non-muscle myosin.
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