Neuronal function and dysfunction of CYFIP2: from actin dynamics to early infantile epileptic encephalopathy
Neuronal function and dysfunction of CYFIP2: from actin dynamics to early infantile epileptic encephalopathy
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DOI：
10.5483/bmbrep.2019.52.5.097
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发表时间：
2019-05
期刊：
影响因子：
3.8
通讯作者：
Yinhua Zhang;Yeunkum Lee;Kihoon Han
中科院分区：
文献类型：
--
作者：
Yinhua Zhang;Yeunkum Lee;Kihoon Han
细胞质FMR 1相互作用蛋白家族（CYFIP 1和CYFIP 2）是进化上保守的蛋白质，最初被鉴定为脆性X智力低下蛋白（FMRP）的结合伴侣，FMRP是一种信使RNA（mRNA）结合蛋白，其缺失导致脆性X综合征。此外，CYFIP是异五聚体WAVE调节复合物（WRC）的关键组分，WRC是神经元肌动蛋白动力学的关键调节剂。因此，CYFIP可能在调节mRNA翻译和肌动蛋白聚合中发挥关键作用，这两个方面与神经元的发育和功能密切相关。然而，与CYFIP1相比，CYFIP2的神经元功能和功能障碍在很大程度上仍然未知，可能是由于CYFIP2和脑部疾病之间的相关性相对较不明确。尽管CYFIP1和CYFIP2之间的氨基酸序列具有高度同源性，但一些体外和动物模型研究表明，CYFIP2具有一些不同于CYFIP1的独特神经元功能。此外，最近的全外显子组测序研究确定了早期婴儿癫痫性脑病（EIEE）患者中CYFIP2的新生热点变体，明确暗示了神经系统疾病中的CYFIP2功能障碍。在这篇综述中，我们强调了这些最近的调查CYFIP 2的神经元功能和功能障碍，并讨论了几个关键的问题仍然关于这个有趣的神经元蛋白。
The cytoplasmic FMR1-interacting protein family (CYFIP1 and CYFIP2) are evolutionarily conserved proteins originally identified as binding partners of the fragile X mental retardation protein (FMRP), a messenger RNA (mRNA)-binding protein whose loss causes the fragile X syndrome. Moreover, CYFIP is a key component of the heteropentameric WAVE regulatory complex (WRC), a critical regulator of neuronal actin dynamics. Therefore, CYFIP may play key roles in regulating both mRNA translation and actin polymerization, which are critically involved in proper neuronal development and function. Nevertheless, compared to CYFIP1, neuronal function and dysfunction of CYFIP2 remain largely unknown, possibly due to the relatively less well established association between CYFIP2 and brain disorders. Despite high amino acid sequence homology between CYFIP1 and CYFIP2, several in vitro and animal model studies have suggested that CYFIP2 has some unique neuronal functions distinct from those of CYFIP1. Furthermore, recent whole-exome sequencing studies identified de novo hot spot variants of CYFIP2 in patients with early infantile epileptic encephalopathy (EIEE), clearly implicating CYFIP2 dysfunction in neurological disorders. In this review, we highlight these recent investigations into the neuronal function and dysfunction of CYFIP2, and also discuss several key questions remaining about this intriguing neuronal protein.