Statistical Laws of Protein Motion in Neuronal Dendritic Trees.
Statistical Laws of Protein Motion in Neuronal Dendritic Trees.
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神经元树突中蛋白质运动的统计规律。
DOI：
10.1016/j.celrep.2020.108391
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发表时间：
2020-11-17
期刊：
影响因子：
8.8
通讯作者：
Tchumatchenko T
中科院分区：
文献类型：
--
作者：
Sartori F;Hafner AS;Karimi A;Nold A;Fonkeu Y;Schuman EM;Tchumatchenko T
在树突树上，神经元分布着数千种蛋白质，这些蛋白质是维持突触功能和可塑性所必需的，需要持续生产并运输到最终目的地。当每个树突支点分裂蛋白质流时，增加支点会减少下游的总蛋白质数量。因此，神经元需要产生更多的蛋白质，以维持远端突触的最低蛋白质数量。结合体外实验和理论框架，我们表明，在细胞膜内扩散的蛋白质在到达下游位置时的效率平均比扩散在细胞质中的蛋白质高35%。当蛋白质在质膜内扩散时，这种优势出现在分支点的向前运动的偏向上。使用3D电子显微镜(EM)数据，我们发现常见蛋白质的金字塔分支统计数据和扩散长度落入最小化总体蛋白质需求的区域。表面蛋白在到达远端位置时比可溶性蛋白更有效，子体半径优化减少了填充树突所需的蛋白质数量，分支点上的子体半径比率是细胞类型特定的高扩散蛋白，未优化半径Sartori等人的额外成本较小。结果表明，表面扩散比细胞质扩散更有效地为远端树突状细胞提供蛋白质。分支点的子体半径分布可以优化远程蛋白质运输，并将填充远端突触所需的蛋白质总数减少数量级。
Across their dendritic trees, neurons distribute thousands of protein species that are necessary for maintaining synaptic function and plasticity and that need to be produced continuously and trafficked to their final destination. As each dendritic branchpoint splits the protein flow, increasing branchpoints decreases the total protein number downstream. Consequently, a neuron needs to produce more proteins to maintain a minimal protein number at distal synapses. Combining in vitro experiments and a theoretical framework, we show that proteins that diffuse within the cell plasma membrane are, on average, 35% more effective at reaching downstream locations than proteins that diffuse in the cytoplasm. This advantage emerges from a bias for forward motion at branchpoints when proteins diffuse within the plasma membrane. Using 3D electron microscopy (EM) data, we show that pyramidal branching statistics and the diffusion lengths of common proteins fall into a region that minimizes the overall protein need. Surface proteins are more efficient at reaching distal sites than soluble proteins Daughter radius optimization reduces the number of proteins needed to populate dendrites Ratios of daughter radii at branchpoints are cell type specific Highly diffusive proteins incur a smaller extra cost for non-optimized radii Sartori et al. show that surface diffusion is more effective at providing proteins for distal dendritic sites than cytoplasmic diffusion. Daughter radius distribution at branchpoints can be optimized for long-range protein transport and reduce the total protein count necessary to populate distal synapses by orders of magnitude.
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