PDF(Pubmed)
Abstract：
Dendritic spines are actin-rich protrusions that receive a signal from the axon at the synapse. Remodeling of cytoskeletal actin is tightly connected to dendritic spine morphology-mediated synaptic plasticity of the neuron. Remodeling of cytoskeletal actin is required for the formation, development, maturation, and reorganization of dendritic spines. Actin filaments are highly dynamic structures with slow-growing/pointed and fast-growing/barbed ends. Very few studies have been conducted on the role of pointed-end binding proteins in the regulation of dendritic spine morphology. In this study, we evaluated the role played by tropomodulin 2 (Tmod2)-a brain-specific isoform, on the dendritic spine re-organization. Tmod2 regulates actin nucleation and polymerization by binding to the pointed end via actin and tropomyosin (Tpm) binding sites. We studied the effects of Tmod2 overexpression in primary hippocampal neurons on spine morphology using confocal microscopy and image analysis. Tmod2 overexpression decreased the spine number and increased spine length. Destroying Tpm-binding ability increased the number of shaft synapses and thin spine motility. Eliminating the actin-binding abilities of Tmod2 increased the number of mushroom spines. Tpm-mediated pointed-end binding decreased F-actin depolymerization, which may positively affect spine stabilization; the nucleation ability of Tmod2 appeared to increase shaft synapses.
摘要：
树突棘是富含肌动蛋白的突起，可在突触处从轴突接收信号。细胞骨架肌动蛋白的重塑与树突棘形态介导的神经元突触可塑性密切相关。细胞骨架肌动蛋白的重塑是形成所必需的，发展,成熟,和树突棘的重组。肌动蛋白丝是具有缓慢生长/尖头和快速生长/带刺末端的高度动态结构。关于尖端结合蛋白在树突棘形态调节中的作用的研究很少。在这项研究中,我们评估了原调节蛋白2（Tmod2）所起的作用-一种脑特异性同工型，树突状脊柱的重组。Tmod2通过肌动蛋白和原肌球蛋白（Tpm）结合位点与尖端结合来调节肌动蛋白的成核和聚合。我们使用共聚焦显微镜和图像分析研究了原代海马神经元中Tmod2过表达对脊柱形态的影响。Tmod2的过度表达减少了脊柱数量并增加了脊柱长度。破坏Tpm结合能力增加了轴突触的数量和脊柱的稀薄运动。消除Tmod2的肌动蛋白结合能力增加了蘑菇棘的数量。Tpm介导的尖端结合减少了F-肌动蛋白解聚，这可能会对脊柱稳定产生积极影响；Tmod2的成核能力似乎增加了轴突触。
