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首页> 外文期刊>Neuron >Asymmetric Clathrin-Mediated Endocytosis Drives Repulsive Growth Cone Guidance
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Asymmetric Clathrin-Mediated Endocytosis Drives Repulsive Growth Cone Guidance

机译：非对称网格蛋白介导的内吞作用驱动排斥生长锥的指导。

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摘要

Asymmetric Ca~(2+) elevations across the axonal growth cone mediate its turning responses to attractive and repulsive guidance cues. Here we show that cla-thrin-mediated endocytosis acts downstream of Ca~(2+) 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 che-morepellent, semaphorin 3A, or by Ca~(2+) signals that mediate repulsive guidance. In contrast, coated pit formation remains symmetric in the presence of attractive Ca~(2+) signals. Inhibition of clathrin-mediated endocytosis abolishes growth cone repulsion, but not attraction, induced by Ca~(2+) 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.
机译：轴突生长锥上不对称的Ca〜（2+）升高介导其对吸引和排斥引导线索的转向反应。在这里，我们表明cla-thrin介导的内吞作用在Ca〜（2+）信号的下游充当生长锥转向的驱动机制。在背根神经节神经元中，通过方向性应用化学驱除剂，信号量3A或介导排斥性引导的Ca〜（2+）信号，促进网格蛋白包被的凹坑在整个生长锥上的分布不对称。相反，在有吸引力的Ca〜（2+）信号存在下，涂层凹坑的形成保持对称。抑制网格蛋白介导的内吞作用消除了Ca〜（2+）或细胞外生理线索诱导的生长锥排斥力，但没有吸引力。此外，生长锥中内吞作用和胞吐作用平衡的不对称扰动足以启动其向具有较少内吞作用或更多胞吐作用的一侧转向。有了我们先前的发现，生长锥吸引涉及不对称的胞吐作用，我们建议膜添加和去除之间的平衡决定了双向轴突引导。

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