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Nrf2 dictates the neuronal survival and differentiation of embryonic zebrafish harboring compromised alanyl-tRNA synthetase
Jin, Binbin1; Xie, Liqin1; Zhan, Dan1; Zhou, Luping1; Feng, Zhi1; He, Jiangyong1; Qin, Jie1; Zhao, Congjian2; Luo, Lingfei1; Li, Li3
2022-09-01
摘要tRNA synthetase deficiency leads to unfolded protein responses in neuronal disorders; however, its function in embryonic neurogenesis remains unclear. This study identified an aars1cq71/cq71 mutant zebrafish allele that showed increased neuronal apoptosis and compromised neurogenesis. aars1 transcripts were highly expressed in primary neural progenitor cells, and their aberration resulted in protein overloading and activated Perk. nfe2l2b, a paralog of mammalian Nfe2l2, which encodes Nrf2, is a pivotal executor of Perk signaling that regulates neuronal phenotypes in aars1cq71/cq71 mutants. Interference of nfe2l2b in nfe2l2b Delta 1/Delta 1 mutants did not affect global larval development. However, aars1cq71/cq71;nfe2l2b Delta 1/Delta 1 mutant embryos exhibited increased neuronal cell survival and neurogenesis compared with their aars1cq71/cq71 siblings. nfe2l2b was harnessed by Perk at two levels. Its transcript was regulated by Chop, an implementer of Perk. It was also phosphorylated by Perk. Both pathways synergistically assured the nuclear functions of nfe2l2b to control cell survival by targeting p53. Our study extends the understanding of tRNA synthetase in neurogenesis and implies that Nrf2 is a cue to mitigate neurodegenerative pathogenesis.
关键词Aars1 Nrf2 UPR Perk Neuronal apoptosis Zebrafish
DOI10.1242/dev.200342
发表期刊DEVELOPMENT
ISSN0950-1991
卷号149期号:17页码:16
通讯作者Luo, Lingfei(lluo@swu.edu.cn) ; Li, Li(lili@cigit.ac.cn)
收录类别SCI
WOS记录号WOS:000874646900001
语种英语