用单粒子追踪递归分析法研究海马神经元表面不同的离子通道
Elucidating distinct ion channel populations on the surface of hippocampal neurons via single-particle tracking recurrence analysis
摘要：
蛋白质和脂质纳米结构域普遍存在于哺乳动物细胞的表面上。特别是，最近已经认识到，离子通道组装成表面纳米团簇在培养的神经元的胞体。然而，这些分子与表面纳米畴的相互作用显示出相当程度的异质性。在这里，我们调查这种异质性，并开发统计工具的基础上复发的个人轨迹，以确定神经元表面的离子通道内的亚群。我们在单分子水平上研究了培养的海马神经元表面K $^+$通道Kv 1.4和Na $^+$通道Nav1.6的动力学。我们发现，这两种分子表达在两种不同的形式与不同的动力学方面的表面相互作用，强调复杂的蛋白质组景观的神经元表面。此外，在这项工作中提出的工具提供了新的方法，用于分析膜nanodomains，瞬态限制，并确定人口内的单粒子轨迹。
英文摘要：
Protein and lipid nanodomains are prevalent on the surface of mammalian cells. In particular, it has been recently recognized that ion channels assemble into surface nanoclusters in the soma of cultured neurons. However, the interactions of these molecules with surface nanodomains display a considerable degree of heterogeneity. Here, we investigate this heterogeneity and develop statistical tools based on the recurrence of individual trajectories to identify subpopulations within ion channels in the neuronal surface. We specifically study the dynamics of the K$^+$ channel Kv1.4 and the Na$^+$ channel Nav1.6 on the surface of cultured hippocampal neurons at the single-molecule level. We find that both these molecules are expressed in two different forms with distinct kinetics with regards to surface interactions, emphasizing the complex proteomic landscape of the neuronal surface. Further, the tools presented in this work provide new methods for the analysis of membrane nanodomains, transient confinement, and identification of populations within single-particle trajectories.
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