Signaling Networks that Regulate Cell Migration
Signaling Networks that Regulate Cell Migration
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DOI：
10.1101/cshperspect.a005959
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发表时间：
2015-08-01
影响因子：
7.2
通讯作者：
Horwitz, Alan Rick
中科院分区：
文献类型：
--
作者：
Devreotes, Peter;Horwitz, Alan Rick
促进细胞迁移的刺激物，如后生动物中的趋化因子、细胞因子和生长因子以及网骨藻中的环AMP，激活控制肌动蛋白细胞骨架和粘附复合物组织的信号传导途径。Rho家族GTP酶是这些途径的关键汇聚点。它们的效应物包括肌动蛋白调节剂，如formins，WASP/WAVE家族和Arp 2/3复合物的成员，以及肌球蛋白II马达蛋白。连接至Rho GTP酶的途径包括Ras GTP酶、TorC 2和PI 3 K。许多参与的分子在细胞内形成梯度，其限定迁移细胞的前部和后部，并且还在相关的细胞行为中建立，例如神经元生长锥延伸和胞质分裂。调节迁移的信号分子可以被整合以提供网络功能的模型。该网络显示出生化兴奋性，被视为沿着细胞皮层沿着传播的自发激活波。这些事件协调细胞运动，并且可以被外部线索偏置以实现定向迁移。
Stimuli that promote cell migration, such as chemokines, cytokines, and growth factors in metazoans and cyclic AMP in Dictyostelium, activate signaling pathways that control organization of the actin cytoskeleton and adhesion complexes. The Rho-family GTPases are a key convergence point of these pathways. Their effectors include actin regulators such as formins, members of the WASP/WAVE family and the Arp2/3 complex, and the myosin II motor protein. Pathways that link to the Rho GTPases include Ras GTPases, TorC2, and PI3K. Many of the molecules involved form gradients within cells, which define the front and rear of migrating cells, and are also established in related cellular behaviors such as neuronal growth cone extension and cytokinesis. The signaling molecules that regulate migration can be integrated to provide a model of network function. The network displays biochemical excitability seen as spontaneous waves of activation that propagate along the cell cortex. These events coordinate cell movement and can be biased by external cues to bring about directed migration.