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Rho guanine nucleotide exchange factor (RGNEF) is a prosurvival factor under stress conditions.
Molecular and Cellular Neuroscience ( IF 3.5 ) Pub Date : 2017-05-13 , DOI: 10.1016/j.mcn.2017.05.003
Kevin Cheung 1 , Cristian A Droppelmann 2 , Adam MacLellan 2 , Ian Cameron 2 , Benjamin Withers 2 , Danae Campos-Melo 2 , Kathryn Volkening 3 , Michael J Strong 4
Affiliation  

Rho guanine nucleotide exchange factor (RGNEF) is a 190kDa RNA binding protein (RBP) that also contains a Dbl/PH domain capable of RhoA activation. Consistent with a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS), RGNEF forms pathological neuronal cytoplasmic inclusions in degenerating spinal motor neurons. To further understand the role of RGNEF in the stress response, we first observed that the expression of RGNEF is upregulated in murine spinal motor neurons following distal sciatic nerve injury. Secondly, in response to in vitro cellular stress (500μM sodium arsenite for 1h; or 400mM sorbitol 1 hour exposure; as an oxidative or osmotic stress, respectively), we observed a significant survival benefit in RGNEF-transfected HEK293T cells. Using deletion constructs, we found that the NH2-terminus domain is essential for this protective effect. Interestingly, we observed that under stress conditions RGNEF associates with Staufen1 positive granules but not TIA-1-positive stress granules. These findings support the hypothesis that RGNEF plays a critical role both in RNA homeostasis and in the response to cell stress.

中文翻译:

Rho鸟嘌呤核苷酸交换因子(RGNEF)是应激条件下的生存因子。

Rho鸟嘌呤核苷酸交换因子(RGNEF)是一个190kDa RNA结合蛋白(RBP),也包含能够激活RhoA的Dbl / PH结构域。与在肌萎缩性侧索硬化症(ALS)发病机理中的关键作用一致,RGNEF在退化的脊髓运动神经元中形成病理性神经元胞浆内含物。为了进一步了解RGNEF在应激反应中的作用,我们首先观察到RGNEF的表达在远端坐骨神经损伤后在鼠脊髓运动神经元中表达上调。其次,响应体外细胞应激(分别暴露500μM亚砷酸钠1h;或暴露400mM山梨糖醇1小时;分别作为氧化应激或渗透应激),我们在RGNEF转染的HEK293T细胞中观察到了显着的存活益处。使用删除结构,我们发现NH2末端域对于这种保护作用至关重要。有趣的是,我们观察到在压力条件下RGNEF与Staufen1阳性颗粒相关,而与TIA-1阳性压力颗粒无关。这些发现支持了RGNEF在RNA稳态和细胞应激反应中均起关键作用的假设。
更新日期:2019-11-01
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