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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Asymmetric redistribution of GABA receptors during GABA gradient sensing by nerve growth cones analyzed by single quantum dot imaging
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Asymmetric redistribution of GABA receptors during GABA gradient sensing by nerve growth cones analyzed by single quantum dot imaging

机译：单量子点成像分析神经生长锥在GABA梯度传感中GABA受体的不对称再分布

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摘要

During development of the nervous system, the tip of a growing axon, the growth cone (GC), must respond accurately to stimuli that direct its growth. This axonal navigation depends on extracellular concentration gradients of numerous guidance cues, including GABA. GCs can detect even weak directional signals, yet the mechanisms underlying this sensitivity remain unclear. Past studies in other eukaryotic chemotactic systems have pointed to the role of the spatial reorganization of the transduction pathway in their sensitive response. Here we have developed a single-molecule assay to observe individual GABA_A receptors (GABA_ARs) in the plasma membrane of nerve GCs subjected to directional stimuli. We report that in the presence of an external GABA gradient GABA_ARs redistribute asymmetrically across the GC toward the gradient source. Single-particle tracking of GABA_ARs shows that the redistribution results from transient interactions between the receptors and the microtubules. Moreover, the relo- calization is accompanied by an enhancement in the asymmetry of intracellular calcium concentration. Altogether, our results reveal a microtubule-dependent polarized reorganization of chemoreceptors at the cell surface and suggest that this polarization serves as an amplification step in GABA gradient sensing by nerve GCs.
机译：在神经系统发育过程中，生长轴突的尖端，即生长锥（GC），必须对引导其生长的刺激做出准确反应。这种轴突导航取决于包括GABA在内的许多指导线索的细胞外浓度梯度。 GC甚至可以检测到微弱的方向信号，但仍不清楚这种敏感性的潜在机制。过去在其他真核趋化系统中的研究指出，转导途径的空间重组在其敏感反应中的作用。在这里，我们已经开发出一种单分子测定法，以观察受到定向刺激的神经GC质膜中的单个GABA_A受体（GABA_ARs）。我们报告说，在存在外部GABA梯度的情况下，GABA_ARs在整个GC中朝着梯度源不对称地重新分布。对GABA_ARs的单粒子跟踪表明，重新分布是由受体与微管之间的短暂相互作用引起的。而且，重新定位伴随着细胞内钙浓度不对称性的增强。总而言之，我们的研究结果揭示了化学感受器在细胞表面的微管依赖性极化重组，并表明该极化充当神经GC在GABA梯度传感中的放大步骤。

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