Pathophysiological Functions of Rnd3/RhoE.
Pathophysiological Functions of Rnd3/RhoE.
复制标题
Rnd3/RhoE 的病理生理功能。
DOI：
10.1002/cphy.c150018
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发表时间：
2015-12-15
影响因子：
5.8
通讯作者：
Chang J
中科院分区：
文献类型：
--
作者：
Jie W;Andrade KC;Lin X;Yang X;Yue X;Chang J
RND3，也被称为RhoE，属于Rho家族小GTP结合蛋白的RND亚类。RND蛋白是独一无二的，因为它们不能从GTP结合的构象转换到GDP结合的构象。尽管对RND3的生物学功能的研究还远未结束，但关于其表达模式、细胞定位和活性的信息是可用的，这些信息可以根据条件的不同而改变。这些研究收集的数据表明，RND3可能不是一个传统的小GTP酶。RND3的基本作用是作为RhoA信号介导的肌动蛋白细胞骨架动力学的内源性拮抗剂，特异性地促进细胞迁移和神经元的极性。此外，RND3还在阻止细胞周期分布、抑制细胞生长、诱导细胞凋亡和分化等方面发挥重要作用。越来越多的数据表明，RND3的异常表达可能是一些全身性疾病的主要原因，尤其是在凋亡性心肌病、发育性心律失常和心力衰竭、脑积水以及肿瘤转移和化疗耐药方面。因此，通过使用合适的模型，更好地了解RND3在不同生理和病理条件下的功能，将为人类多种疾病的起源和治疗提供新的视角。
Rnd3, also known as RhoE, belongs to the Rnd subclass of the Rho family of small GTP-binding proteins. Rnd proteins are unique due to their inability to switch from a GTP-bound to GDP-bound conformation. Even though studies of the biological function of Rnd3 are far from being concluded, information is available regarding its expression pattern, cellular localization, and its activity, which can be altered depending on the conditions. The compiled data from these studies implies that Rnd3 may not be a traditional small GTPase. The basic role of Rnd3 is to report as an endogenous antagonist of RhoA signaling-mediated actin cytoskeleton dynamics, which specifically contributes to cell migration and neuron polarity. In addition, Rnd3 also plays a critical role in arresting cell cycle distribution, inhibiting cell growth, and inducing apoptosis and differentiation. Increasing data have shown that aberrant Rnd3 expression may be the leading cause of some systemic diseases; particularly highlighted in apoptotic cardiomyopathy, developmental arrhythmogenesis and heart failure, hydrocephalus, as well as tumor metastasis and chemotherapy resistance. Therefore, a better understanding of the function of Rnd3 under different physiological and pathological conditions, through the use of suitable models, would provide a novel insight into the origin and treatment of multiple human diseases.