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Filopodia Conduct Target Selection in Cortical Neurons Using Differences in Signal Kinetics of a Single Kinase

机译:Filopodia使用单一激酶的信号动力学差异进行皮质神经元的靶选择

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摘要

Dendritic filopodia select synaptic partner axons by interviewing the cell surface of potential targets, but how filopodia decipher the complex pattern of adhesive and repulsive molecular cues to find appropriate contacts is unknown. Here, we demonstrate in cortical neurons that a single cue is sufficient for dendritic filopodia to reject or select specific axonal contacts for elaboration as synaptic sites. Super-resolution and live-cell imaging reveals that EphB2 is located in the tips of filopodia and at nascent synaptic sites. Surprisingly, a genetically encoded indicator of EphB kinase activity, unbiased classification, and a photoactivatable EphB2 reveal that simple differences in the kinetics of EphB kinase signaling at the tips of filopodia mediate the choice between retraction and synaptogenesis. This may enable individual filopodia to choose targets based on differences in the activation rate of a single tyrosine kinase, greatly simplifying the process of partner selection and suggesting a general principle.
机译:树突式Filopodia通过面试潜在目标的细胞表面选择突触伴侣轴突,但是氟化绦虫如何破译粘合剂和排斥分子提示的复杂模式是如何找到适当的触点。在这里,我们在皮质神经元中证明了单个提示足以用于树突状氟化绦虫,以拒绝或选择用于突触位点的特定轴突触点。超分辨率和活细胞成像显示EphB2位于氟覆的尖端和新生突触位点。令人惊讶的是,Ephb激酶活性的遗传编码指示剂,无偏见的分类和可光活化的EphB2揭示了Ephb激酶信号传导在Filopodia尖端中的简单差异介导收缩和突触突触之间的选择。这可能使单个氟化碳基于单个酪氨酸激酶的激活率的差异来选择靶标,大大简化了合作伙伴选择的过程并提出了一般原则。

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