Bilateral crosstalk of rho- and extracellular-signal-regulated-kinase (ERK) pathways is confined to an unidirectional mode in spinal muscular atrophy (SMA)
Bilateral crosstalk of rho- and extracellular-signal-regulated-kinase (ERK) pathways is confined to an unidirectional mode in spinal muscular atrophy (SMA)
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DOI：
10.1016/j.cellsig.2013.11.027
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发表时间：
2014-03-01
影响因子：
4.8
通讯作者：
Claus, Peter
中科院分区：
文献类型：
--
作者：
Hensel, Niko;Stockbruegger, Inga;Claus, Peter
Rho激酶（ROCK）以及细胞外信号调节激酶（ERK）控制肌动蛋白细胞骨架组织，从而调节细胞形态的动态变化。在神经元中，轴突引导和神经突生长等运动过程需要对上游通路进行精细调节。在这里，我们展示了神经元中的双边 ROCK-ERK 信息流。在神经退行性疾病脊髓性肌萎缩症 (SMA) 模型中，这一过程转向单向串扰，最终导致神经突生长失调。由于这两种途径都与 SMA 具有治疗相关性，因此我们的结果支持将 ROCK/ERK 靶向组合作为未来的治疗策略。 (C) 2013 Elsevier Inc. 保留所有权利。
Rho-kinase (ROCK) as well as extracellular signal regulated kinase (ERK) control actin cytoskeletal organization thereby regulating dynamic changes of cellular morphology. In neurons, motility processes such as axonal guidance and neurite outgrowth demand a fine regulation of upstream pathways. Here we demonstrate a bilateral ROCK-ERK information flow in neurons. This process is shifted towards an unidirectional crosstalk in a model of the neurodegenerative disease Spinal Muscular Atrophy (SMA), ultimately leading to neurite outgrowth dysregulations. As both pathways are of therapeutic relevance for SMA, our results argue for a combinatorial ROCK/ERK-targeting as a future treatment strategy. (C) 2013 Elsevier Inc. All rights reserved.