Structural organization of the actin-spectrin-based membrane skeleton in dendrites and soma of neurons
Structural organization of the actin-spectrin-based membrane skeleton in dendrites and soma of neurons
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DOI：
10.1073/pnas.1705043114
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发表时间：
2017-08-08
影响因子：
11.1
通讯作者：
Zhuang, Xiaowei
中科院分区：
文献类型：
--
作者：
Han, Boran;Zhou, Ruobo;Zhuang, Xiaowei
肌动蛋白、谱蛋白及其相关分子在神经元中形成膜相关周期性骨架（MPS）。在MPS中，短的肌动蛋白丝被肌动蛋白盖住，形成环绕神经突周长的环状结构，这些环状结构通过谱蛋白四聚体周期性地沿着神经突间隔，形成准一维晶格结构。这种一维MPS结构最初是在轴突中观察到的，广泛存在于轴突中，几乎跨越了成熟神经元的整个轴突轴。在树突中也观察到这种1D MPS，但其存在的程度以及如何在树突中发展尚不清楚。目前还不清楚神经元中是否存在膜骨架的其他结构形式。本研究利用超分辨率成像技术，研究了不同发育阶段海马神经元树突和体细胞中谱蛋白、肌动蛋白和内收蛋白（一种肌动蛋白封盖蛋白）的空间组织，并与轴突中的结果进行了比较。我们观察到，1D MPS存在于相对成熟的神经元的大部分树突区域，但这种结构在树突中发育较慢，并且在轴突中形成的倾向较低。此外，我们观察到谱蛋白、肌动蛋白和内收蛋白也在体突室中形成二维多边形晶格结构，类似于扩大的红细胞膜骨架结构。这种二维晶格结构在体细胞和树突中的发展也比轴突中的一维MPS的发展要慢得多。这些结果表明，膜骨架结构在神经元的不同亚室之间受到不同的调节。
Actin, spectrin, and associated molecules form a membrane-associated periodic skeleton (MPS) in neurons. In the MPS, short actin filaments, capped by actin-capping proteins, form ring-like structures that wrap around the circumference of neurites, and these rings are periodically spaced along the neurite by spectrin tetramers, forming a quasi-1D lattice structure. This 1D MPS structure was initially observed in axons and exists extensively in axons, spanning nearly the entire axonal shaft of mature neurons. Such 1D MPS was also observed in dendrites, but the extent to which it exists and how it develops in dendrites remain unclear. It is also unclear whether other structural forms of the membrane skeleton are present in neurons. Here, we investigated the spatial organizations of spectrin, actin, and adducin, an actin-capping protein, in the dendrites and soma of cultured hippocampal neurons at different developmental stages, and compared results with those obtained in axons, using superresolution imaging. We observed that the 1D MPS exists in a substantial fraction of dendritic regions in relatively mature neurons, but this structure develops slower and forms with a lower propensity in dendrites than in axons. In addition, we observed that spectrin, actin, and adducin also form a 2D polygonal lattice structure, resembling the expanded erythrocyte membrane skeleton structure, in the somatodendritic compartment. This 2D lattice structure also develops substantially more slowly in the soma and dendrites than the development of the 1D MPS in axons. These results suggest membrane skeleton structures are differentially regulated across different subcompartments of neurons.