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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Heterogeneity of AMPA receptor trafficking and molecular interactions revealed by superresolution analysis of live cell imaging
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Heterogeneity of AMPA receptor trafficking and molecular interactions revealed by superresolution analysis of live cell imaging

机译：通过活细胞成像的超分辨率分析揭示AMPA受体运输的异质性和分子相互作用

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摘要

Simultaneous tracking of many thousands of individual particles in live cells is possible now with the advent of high-density super-resolution imaging methods. We present an approach to extract local biophysical properties of cell-particle interaction from such newly acquired large collection of data. Because classical methods do not keep the spatial localization of individual trajectories, it is not possible to access localized biophysical parameters. In contrast by combining the high-density superresolution imaging data with the present analysis, we determine the local properties of protein dynamics. We specifically focus on AMPA receptor (AMPAR) trafficking and estimate the strength of their molecular interaction at the subdiffraction level in hippocampal dendrites. These interactions correspond to attracting potential wells of large size, showing that the high density of AMPARs is generated by physical interactions with an ensemble of cooperative membrane surface binding sites, rather than molecular crowding or aggregation, which is the case for the membrane viral glycoprotein VSVG. We further show that AMPARs can either be pushed in or out of dendritic spines. Finally, we characterize the recurrent step of influenza trajectories. To conclude, the present analysis allows the identification of the molecular organization responsible for the heterogeneities of random trajectories in cells.
机译：随着高密度超分辨率成像方法的出现，现在可以同时追踪活细胞中成千上万的单个粒子。我们提出了一种从这种新近获得的大量数据中提取细胞-颗粒相互作用的局部生物物理特性的方法。因为经典方法不能保持单个轨迹的空间局部性，所以不可能访问局部的生物物理参数。相比之下，通过将高密度超分辨率成像数据与当前分析相结合，我们确定了蛋白质动力学的局部性质。我们特别关注AMPA受体（AMPAR）的运输，并在海马树突状细胞的亚衍射水平上估计其分子相互作用的强度。这些相互作用对应于吸引大尺寸的潜在孔，表明AMPARs的高密度是通过与协作膜表面结合位点的整体相互作用而不是分子拥挤或聚集而产生的，膜病毒糖蛋白VSVG就是这种情况。我们进一步表明，AMPAR可以被推入或拉出树突棘。最后，我们描述了流感轨迹的复发步骤。总而言之，本分析允许鉴定负责细胞中随机轨迹异质性的分子组织。

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  • 作者

    Nathanael Hoze; Deepak Nair; Eric Hosy; Christian Sieben; Sutiana Manley; Andreas Herrmann; Jean-Baptiste Sibarita; Daniel Choquet; David Holcman;

  • 作者单位

    Group of Computational Biology and Applied Mathematics, Institute of Biology, Ecole Normale Superieure, 46 Rue d'Ulm, 75005 Paris, France;

    Group of Computational Biology and Applied Mathematics, Institute of Biology, Ecole Normale Superieure, 46 Rue d'Ulm, 75005 Paris, France;

    Universite de Bordeaux, Institut Interdisciplinaire des Neurosciences, Unite Mixte de Recherche 5297, F-33000 Bordeaux, France;

    Centre National de la Recherche Scientifique, Institut Interdisciplinaire des Neurosciences, Unite Mixte de Recherche 5297, F-33000 Bordeaux, France;

    Laboratory of Experimental Biophysics, Ecole Polytechnique Federale de Lausanne, 1005 Lausanne, Switzerland;

    Centre National de la Recherche Scientifique, Institut Interdisciplinaire des Neurosciences, Unite Mixte de Recherche 5297, F-33000 Bordeaux, France;

    Universite de Bordeaux, Institut Interdisciplinaire des Neurosciences, Unite Mixte de Recherche 5297, F-33000 Bordeaux, France;

    Universite de Bordeaux, Institut Interdisciplinaire des Neurosciences, Unite Mixte de Recherche 5297, F-33000 Bordeaux, France;

    Group of Computational Biology and Applied Mathematics, Institute of Biology, Ecole Normale Superieure, 46 Rue d'Ulm, 75005 Paris, France;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    stochastic analysis of trajectories; dendritic spines and synapses; single particle tracking; confined diffusion;

    机译：轨迹的随机分析;树突棘和突触;单粒子跟踪;限制扩散;

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