Abstract:
The cytohesin proteins, consisting of four closely related members (cytohesins-1, -2, -3, and -4), are a subfamily of the Sec7 domain-containing guanine nucleotide exchange factors for ADP ribosylation factors (Arfs), which are critical regulators of membrane trafficking and actin cytoskeleton remodeling. Recent advances in molecular biological techniques and the development of a specific pharmacological inhibitor for cytohesins, SecinH3, have revealed the functional involvement of the cytohesin-Arf pathway in diverse neuronal functions from the formation of axons and dendrites, axonal pathfinding, and synaptic vesicle recycling, to pathophysiological processes including chronic pain and neurotoxicity induced by proteins related to neurodegenerative disorders, such as amyotrophic lateral sclerosis and Alzheimer\'s disease. Here, we review the physiological and pathological roles of the cytohesin-Arf pathway in neurons and discuss the future directions of this research field.
摘要:
胞浆蛋白,由四个密切相关的成员组成(cytohesins-1、-2、-3和-4),是ADP核糖基化因子(Arfs)的含Sec7结构域的鸟嘌呤核苷酸交换因子的亚家族,它们是膜运输和肌动蛋白细胞骨架重塑的关键调节因子。分子生物学技术的最新进展和细胞胶质素特异性药理抑制剂的开发,SecinH3,已经揭示了cytohesin-Arf途径在轴突和树突形成的多种神经元功能中的功能参与,轴突寻路,和突触小泡循环,病理生理过程,包括与神经退行性疾病相关的蛋白质引起的慢性疼痛和神经毒性,如肌萎缩侧索硬化症和阿尔茨海默病。这里,本文综述了cyhesin-Arf通路在神经元中的生理和病理作用,并对该领域的研究方向进行了展望。