Aagab is required for zebrafish larval development by regulating neural activity

Shihui Ding; Tursunjan Aziz; Anming Meng; Shunji Jia

doi:10.1016/j.jgg.2024.01.003

Volume 51 Issue 6

Jun. 2024

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Article Navigation > Journal of Genetics and Genomics > 2024 > 51(6): 630-641

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Aagab is required for zebrafish larval development by regulating neural activity

doi: 10.1016/j.jgg.2024.01.003

a. State Key Laboratory of Membrane Biology, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China;
b. Guangzhou Laboratory, Guangzhou, Guangdong 510320, China;
c. State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China

Funds:

We are grateful to the members of Dr. Anming Meng laboratory and Dr. Shunji Jia laboratory for suggestions and comments on this work, especially John Xiao He Li (helpful discussion, suggestion on manuscript) and Zheng Jiang (helpful discussion, wild-type Tg(huc:GFP) and Tg(huc:h2b-GCamp6s) fish lines maintenance). Tg(huc:GRAB-NE2m) zebrafish was a gift from the lab of Dr. Jiu-lin Du (CEBSIT, CAS) and Dr. Yulong Li (Peking University). We thank Dr. Weixiang Guo, Dr. Bai-bing Zhang, Dr. Fu-ning Li, Dr. Changmei Zhang, Dr. Likun Yao, and Lei Wang for helpful discussion or technical guidance. Behavioral tracking system DanioVision (Noldus) was offered by the lab of Dr. Lei Tao (Tsinghua University). This work was financially supported by the National Natural Science Foundation of China (#92254302, #32293202, #2019YFA0801400 to S. J., and #31988101 to A. M.).

Received Date: 2023-10-12
Accepted Date: 2024-01-15
Rev Recd Date: 2024-01-13

Available Online: 2025-06-06

Publish Date: 2024-01-20

Abstract

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 γ-adaptin 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 aagab in zebrafish, revealing impaired swimming and early larval mortality. Given the high expression level of aagab 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 on neurological disorders.
- Aagab,
- Endocytosis,
- Neural activity,
- Synaptic transmitter release,
- Zebrafish

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References(29)

References

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