Role of septin cytoskeleton in spine morphogenesis and dendrite development in neurons
Role of septin cytoskeleton in spine morphogenesis and dendrite development in neurons
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DOI：
10.1016/j.cub.2007.09.039
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发表时间：
2007-10-23
期刊：
影响因子：
9.2
通讯作者：
Sheng, Morgan
中科院分区：
文献类型：
--
作者：
Tada, Tomoko;Simonetta, Alyson;Sheng, Morgan
Septins是GTP结合蛋白，其在体外和体内折叠成异聚体细丝并形成微观束或环状结构。由于这些性质及其与膜、F-肌动蛋白和微管结合的能力，septins通常被认为是细胞骨架组分[1，2]。已知隔膜蛋白在胞质分裂、膜运输和作为结构支架中发挥作用;然而，它们在神经元中的功能知之甚少。通过对脑的突触后密度（PSD）部分的质谱分析发现了septin家族的许多成员，包括Septin 7（Sept 7），这表明septin在神经元中可能具有突触后功能。我们报告说，Sept 7是本地化的基础上的树突状突起和树突状分支点在培养的海马神经元的分布让人想起septin本地化的芽颈芽殖酵母。Sept 7的过表达增加了树突分支和树突突起的密度，而RNA干扰（RNAi）介导的Sept 7敲低导致树突树枝化减少和更大比例的未成熟突起。这些数据表明，在神经元成熟过程中，Sept 7对棘形态发生和树突发育至关重要。
Septins are GTP-binding proteins that polymerize into heteromeric filaments and form microscopic bundles or ring structures in vitro and in vivo. Because of these properties and their ability to associate with membrane, F-actin, and microtubules, septins have been generally regarded as cytoskeletal components [1, 2]. Septins are known to play roles in cytokinesis, in membrane trafficking, and as structural scaffolds; however, their function in neurons is poorly understood. Many members of the septin family, including Septin 7 (Sept7), were found by mass-spectrometry analysis of postsynaptic density (PSD) fractions of the brain [3, 4], suggesting a possible postsynaptic function of septins in neurons. We report that Sept7 is localized at the base of dendritic protrusions and at dendritic branch points in cultured hippocampal neurons-a distribution reminiscent of septin localization in the bud neck of budding yeast. Overexpression of Sept7 increased dendrite branching and the density of dendritic protrusions, whereas RNA interference (RNAi)-mediated knockdown of Sept7 led to reduced dendrite arborization and a greater proportion of immature protrusions. These data suggest that Sept7 is critical for spine morphogenesis and dendrite development during neuronal maturation.