Switching direction in electric-signal-induced cell migration by cyclic guanosine monophosphate and phosphatidylinositol signaling
Switching direction in electric-signal-induced cell migration by cyclic guanosine monophosphate and phosphatidylinositol signaling
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DOI：
10.1073/pnas.0809974106
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发表时间：
2009-04-21
影响因子：
11.1
通讯作者：
Ueda, Masahiro
中科院分区：
文献类型：
--
作者：
Sato, Masayuki J.;Kuwayama, Hidekazu;Ueda, Masahiro
在细胞外引导信号的作用下，细胞运动中的吸引力和排斥性迁移之间的切换在不同类型的细胞中被发现，并且是细胞和发育过程中移位的重要细胞功能。在这里，我们表明，在Dictyostelials细胞的趋电过程中的优先迁移方向可以通过基因调控鸟苷环化酶(GCase)和环鸟苷(CGMP)结合蛋白C(GBPC)并结合抑制磷脂酰肌醇-3-羟基激酶(PI3Ks)来逆转。在直流电场作用下，PI3K依赖的途径参与了阴极定向迁移。可溶性GCase(SGC)和gbpc的催化结构域也通过cGMP介导阴极导向信号，而sGC的N-末端结构域通过抑制PI3Ks和cGMP的产生来介导阳极导向信号。这些观察提供了趋电性中定向转换所需的基因的鉴定，并表明对电信号的并行处理，其中多个信号通路作用于引导细胞向阴极或阳极移动，用于确定迁移的方向。
Switching between attractive and repulsive migration in cell movement in response to extracellular guidance cues has been found in various cell types and is an important cellular function for translocation during cellular and developmental processes. Here we show that the preferential direction of migration during electrotaxis in Dictyostelium cells can be reversed by genetically modulating both guanylyl cyclases (GCases) and the cyclic guanosine monophosphate (cGMP)-binding protein C (GbpC) in combination with the inhibition of phosphatidylinositol-3-OH kinases (PI3Ks). The PI3K-dependent pathway is involved in cathode-directed migration under a direct-current electric field. The catalytic domains of soluble GCase (sGC) and GbpC also mediate cathode-directed signaling via cGMP, whereas the N-terminal domain of sGC mediates anode-directed signaling in conjunction with both the inhibition of PI3Ks and cGMP production. These observations provide an identification of the genes required for directional switching in electrotaxis and suggest that a parallel processing of electric signals, in which multiple-signaling pathways act to bias cell movement toward the cathode or anode, is used to determine the direction of migration.