中国科学院遗传与发育生物学研究所Shunji Jia团队发现，Aagab是斑马鱼幼体发育所需。2024年1月20日，《遗传学报》在线发表了这一最新研究成果。

研究人员报道了α-和γ-adaptin结合蛋白（aagab）在斑马鱼发育过程中的生物学功能。研究人员在斑马鱼体内建立了一个aagab基因功能缺失突变体，发现该突变体游泳能力受损，幼体早期死亡。鉴于aagab基因在大脑中的高表达水平，研究人员对其在神经系统中的生理作用进行了探究。aagab突变体的视神经构造神经元中的钙离子反应和局部场电位表现出抑制作用，这与aagab突变体的视神经构造神经髓鞘中神经递质（如去甲肾上腺素）释放减少的情况一致。在突变体中过表达aagab mRNA或神经刺激剂处理可恢复神经递质释放、钙反应、游泳能力和存活率。

此外，观察结果表明，在AAGAB敲低的分化神经母细胞瘤细胞中，FM 1-43的释放延迟，这可能与网格蛋白介导的突触囊泡再循环缺陷有关。总之，这项研究强调了Aagab在神经生物学中的重要意义，并提示了它对神经系统疾病的潜在影响。

研究人员表示，网格蛋白介导的内吞作用与多种生理过程有关，包括营养摄取、信号转导、突触囊泡再循环、细胞极性的维持以及抗原呈递。尽管人们已经知道aagab是促进网格蛋白介导的内吞作用的关键调节因子，但它的生理功能仍然难以捉摸。

附：英文原文

Title: Aagab is required for zebrafish larval development by regulating neural activity

Author: anonymous

Issue&Volume: 2024/01/20

Abstract: Clathrin-mediated endocytosis has been implicated in various physiological processes, including nutrient uptake, signal transduction, synaptic vesicle recycling, maintenance of cell polarity, and antigen presentation. Despite prior knowledge of its importance as a key regulator in promoting clathrin-mediated endocytosis, the physiological function of α and γadaptin binding protein (aagab) remains elusive. In this study, we investigate the biological function of aagab during zebrafish development. We establish a loss-of-function mutant of the aagab gene in zebrafish, revealing impaired swimming and early larval mortality. Given the high expression level of the aagab gene in the brain, we probe into its physiological role in the nervous system. aagab mutants display subdued calcium responses and local field potential in the optic tectal neurons, aligning with reduced neurotransmitter release (e.g., norepinephrine) in the tectal neuropil of aagab mutants. Overexpressing aagab mRNA or nervous stimulant treatment in mutants restores neurotransmitter release, calcium responses, swimming ability, and survival. Furthermore, our observations show delayed release of FM 1-43 in AAGAB knockdown differentiated neuroblastoma cells, pointing towards a probable link to defective clathrin-mediated synaptic vesicle recycling. In conclusion, our study underscores the significance of Aagab in neurobiology and suggests its potential impacts in neurological disorders.

DOI: 10.1016/j.jgg.2024.01.003

Source: https://www.sciencedirect.com/science/article/abs/pii/S1673852724000134