Sakagami Hiroyuki
Department of Anatomy, Kitasato University School of Medicine.
Tohoku J Exp Med. 2008 Mar;214(3):191-8. doi: 10.1620/tjem.214.191.
ADP ribosylation factor 6 (ARF6) is a member of the ARF family of small GTPases, which mediates a variety of neuronal functions accompanying the structural changes of developing and mature neurons through its regulation of actin cytoskeleton reorganization and membrane traffic. The activation of ARF6 is strictly regulated by guanine nucleotide exchange factors (GEFs). The EFA6 family is the first member that was identified to be a specific GEF for ARF6 and comprises four structurally related polypeptides (EFA6A, EFA6B, EFA6C and EFA6D). Since the cellular and subcelllular localization of GEFs is a critical determinant for the spatiotemporal activation of ARF6 in neurons, I have focused on the EFA6 family from the anatomical point of view to understand the neuronal functions of ARF6. Three members of the EFA6 family (EFA6A, EFA6C and EFA6D) are abundantly expressed in the mouse brain with distinct spatiotemporal patterns. Interestingly, they are enriched particularly in the postsynaptic density fraction, shedding light on the importance of the EFA-ARF6 pathway in neuronal synapses. Here, I will review the recent advances in the expression and functions of the EFA6 family in the nervous system.
ADP核糖基化因子6（ARF6）是小GTP酶ARF家族的成员，它通过调节肌动蛋白细胞骨架重组和膜运输，介导发育中和成熟神经元结构变化所伴随的多种神经元功能。ARF6的激活受到鸟嘌呤核苷酸交换因子（GEF）的严格调控。EFA6家族是首个被鉴定为ARF6特异性GEF的成员，由四种结构相关的多肽（EFA6A、EFA6B、EFA6C和EFA6D）组成。由于GEF的细胞和亚细胞定位是神经元中ARF6时空激活的关键决定因素，我从解剖学角度聚焦于EFA6家族，以了解ARF6的神经元功能。EFA6家族的三个成员（EFA6A、EFA6C和EFA6D）在小鼠脑中大量表达，具有独特的时空模式。有趣的是，它们尤其富集于突触后致密组分中，这揭示了EFA-ARF6通路在神经元突触中的重要性。在此，我将综述EFA6家族在神经系统中表达和功能的最新进展。
