Spastin-interacting protein NA14/SSNA1 functions in cytokinesis and axon development.
Spastin-interacting protein NA14/SSNA1 functions in cytokinesis and axon development.
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痉挛相互作用蛋白Na14/SSNA1在细胞因子和轴突发育中起作用。
DOI：
10.1371/journal.pone.0112428
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Blackstone C
中科院分区：
文献类型：
--
作者：
Goyal U;Renvoisé B;Chang J;Blackstone C
遗传性痉挛性截瘫（HSP）是一组遗传多样的遗传性神经系统疾病（SPG 1 -72），其主要特征是由于皮质脊髓运动神经元的长度依赖性轴突病引起的下肢痉挛。最常见的常染色体显性HSP形式是由SPG 4基因产物spastin的突变引起的。这是一种与多种细胞活性（AAA）蛋白相关的ATP酶，可结合并切断微管。虽然spastin参与细胞质分裂、内体微管和轴突发育等重要的细胞过程，但其在HSP发病机制中的作用仍不清楚。Spastin在细胞中与NA 14蛋白相互作用，NA 14蛋白是干燥综合征（核自身抗原1; SSNA 1）中自身抗体的主要靶点。我们的分析内源性痉挛和NA 14蛋白在HeLa细胞和大鼠皮层神经元在原代培养揭示了一个明确的分布，这两种蛋白质的中心体，NA 14定位专门的中心粒。在细胞系中稳定的NA 14敲低显著影响细胞分裂，特别是胞质分裂。此外，NA 14在神经元中的过表达显著增加轴突生长和分支，同时也增强神经元分化。我们推测，NA 14可能作为一个适配器蛋白调节痉挛定位到中心体，时空调节微管切断活动的痉挛，这是特别关键的细胞周期和神经元发育。
Hereditary spastic paraplegias (HSPs) are a genetically diverse group of inherited neurological disorders (SPG1-72) with the cardinal feature of prominent lower-extremity spasticity due to a length-dependent axonopathy of corticospinal motor neurons. The most frequent form of autosomal dominant HSP results from mutations of the SPG4 gene product spastin. This is an ATPase associated with diverse cellular activities (AAA) protein that binds to and severs microtubules. While spastin participates in crucial cellular processes such as cytokinesis, endosomal tubulation, and axon development, its role in HSP pathogenesis remains unclear. Spastin interacts in cells with the NA14 protein, a major target for auto-antibodies in Sjögren's syndrome (nuclear autoantigen 1; SSNA1). Our analysis of endogenous spastin and NA14 proteins in HeLa cells and rat cortical neurons in primary culture revealed a clear distribution of both proteins to centrosomes, with NA14 localizing specifically to centrioles. Stable NA14 knockdown in cell lines dramatically affected cell division, in particular cytokinesis. Furthermore, overexpression of NA14 in neurons significantly increased axon outgrowth and branching, while also enhancing neuronal differentiation. We postulate that NA14 may act as an adaptor protein regulating spastin localization to centrosomes, temporally and spatially regulating the microtubule-severing activity of spastin that is particularly critical during the cell cycle and neuronal development.
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影响因子：
13.9
作者：
Blackstone C
通讯作者：
Blackstone C
影响因子：
5.2
作者：
Denton, Kyle R.;Lei, Ling;Grenier, Jeremy;Rodionov, Vladimir;Blackstone, Craig;Li, Xue-Jun
通讯作者：
Li, Xue-Jun
DOI：
10.1038/nrn2946
发表时间：
2011-01
期刊：
Nature reviews. Neuroscience
影响因子：
--
作者：
Blackstone C;O'Kane CJ;Reid E
通讯作者：
Reid E
影响因子：
3.5
作者：
Errico, A;Claudiani, P;Rugarli, EI
通讯作者：
Rugarli, EI
影响因子：
64.8
作者：
Andersen, JS;Wilkinson, CJ;Mann, M
通讯作者：
Mann, M