Asymmetric Clathrin-Mediated Endocytosis Drives Repulsive Growth Cone Guidance
Asymmetric Clathrin-Mediated Endocytosis Drives Repulsive Growth Cone Guidance
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DOI：
10.1016/j.neuron.2010.04.007
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发表时间：
2010-05-13
期刊：
影响因子：
16.2
通讯作者：
Kamiguchi, Hiroyuki
中科院分区：
文献类型：
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作者：
Tojima, Takuro;Itofusa, Rurika;Kamiguchi, Hiroyuki
在轴突生长锥上不对称的Ca2+升高介导其对吸引和排斥引导信号的转向反应。在这里，我们发现网格蛋白介导的内吞作用在Ca2+信号的下游作为生长锥转向的驱动机制。在背根神经节神经元中，定向应用化学驱避剂、信号蛋白3A或介导排斥引导的Ca2+信号，促进了网格蛋白包被凹坑在生长锥上的不对称形成。相比之下，在有吸引力的Ca2+信号存在的情况下，涂覆的坑形成保持对称。抑制网格蛋白介导的内吞作用消除了由Ca2+或细胞外生理信号引起的生长锥排斥，而不是吸引。此外，生长锥内吞和胞吐平衡的不对称扰动足以使其转向胞吞较少或胞吐较多的一侧。根据我们之前的发现，生长锥吸引涉及不对称胞吐，我们提出膜添加和去除之间的平衡决定了双向轴突引导。
Asymmetric Ca2+ elevations across the axonal growth cone mediate its turning responses to attractive and repulsive guidance cues. Here we show that clathrin-mediated endocytosis acts downstream of Ca2+ signals as driving machinery for growth cone turning. In dorsal root ganglion neurons, the formation of clathrin-coated pits is facilitated asymmetrically across the growth cone by a directionally applied chemorepellent, semaphorin 3A, or by Ca2+ signals that mediate repulsive guidance. In contrast, coated pit formation remains symmetric in the presence of attractive Ca2+ signals. Inhibition of clathrin-mediated endocytosis abolishes growth cone repulsion, but not attraction, induced by Ca2+ or extracellular physiological cues. Furthermore, asymmetric perturbation of the balance of endocytosis and exocytosis in the growth cone is sufficient to initiate its turning toward the side with less endocytosis or more exocytosis. With our previous finding that growth cone attraction involves asymmetric exocytosis, we propose that the balance between membrane addition and removal dictates bidirectional axon guidance.