Effects of Tropomodulin 2 on Dendritic Spine Reorganization and Dynamics.
Effects of Tropomodulin 2 on Dendritic Spine Reorganization and Dynamics.
复制标题
DOI：
10.3390/biom13081237
复制
发表时间：
2023-08-11
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
树突棘是富含肌动蛋白的突起，可以从突触的轴突接收信号。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。树突棘的形成、发育、成熟和重组需要细胞骨架肌动蛋白的重塑。肌动蛋白丝是高度动态的结构，末端生长缓慢/尖和快速/倒刺。目前关于尖端结合蛋白在树突棘形态调控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）在树突棘重组中的作用，Tmod2是一种脑特异性亚型。Tmod2通过肌动蛋白和原肌球蛋白（Tpm）结合位点与尖端结合，调节肌动蛋白成核和聚合。我们利用共聚焦显微镜和图像分析研究了Tmod2过表达海马初级神经元对脊柱形态的影响。Tmod2过表达使脊柱数目减少，脊柱长度增加。破坏tpm结合能力增加了轴突触的数量和细棘的运动性。消除Tmod2的肌动蛋白结合能力增加了蘑菇棘的数量。tpm介导的末端结合减少了f -肌动蛋白解聚，可能对脊柱稳定有积极影响；Tmod2的成核能力似乎增加了轴突触。
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.
登录
查看更多内容
影响因子：
16.2
作者：
Berry KP;Nedivi E
通讯作者：
Nedivi E
影响因子：
5.9
作者：
Colpan M;Iwanski J;Gregorio CC
通讯作者：
Gregorio CC
影响因子：
64.5
作者：
Ahuja, Rashmi;Pinyol, Roser;Qualmann, Britta
通讯作者：
Qualmann, Britta
影响因子：
4.8
作者：
Helgeson, Luke A.;Prendergast, Julianna G.;Nolen, Brad J.
通讯作者：
Nolen, Brad J.
影响因子：
5.3
作者：
Korkotian, E;Segal, M
通讯作者：
Segal, M