Yang Shuyan, Cao Shanhu, Xu Xuebing, Li Quan, Li Jianting, Guo Jin, Wang Fang, Bao Yihua, Jiang Zean, Zhang Ting, Wang Li, Sun Shaoguang
Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing 100020, China.
Department of Biochemistry and Molecular Biology, Key Laboratory of Medical Biotechnology of Hebei Province, Cardiovascular Medical Science Center, Hebei Medical University, Shijiazhuang 050017, China.
iScience. 2023 Jul 29;26(9):107516. doi: 10.1016/j.isci.2023.107516. eCollection 2023 Sep 15.
Adducin 1 (Add1) is known as a membrane cytoskeletal protein, but its nuclear function remains unclear. In this study, we generated -deficient zebrafish to investigate its role in hematopoiesis. Lack of impaired both primitive and definitive hematopoiesis, preventing healthy erythrocyte development. RNA sequencing revealed activation of the p53 pathway in -depleted erythroblast cells, leading to apoptosis at the 14-somites stage and 24 hpf. Interestingly, partial rescue of the anemic phenotype and apoptosis was observed with insufficiency. Mechanistically, ADD1 was found to regulate promoter activity. These findings demonstrate that Add1 plays a crucial role in zebrafish erythropoiesis, involving the p53-mediated apoptotic pathway, expanding its regulatory role beyond cytoskeletal functions.
内收蛋白1（Add1）作为一种膜细胞骨架蛋白已为人所知，但其核功能仍不清楚。在本研究中，我们构建了Add1缺陷型斑马鱼，以研究其在造血过程中的作用。Add1的缺失损害了原始造血和定向造血，阻碍了健康红细胞的发育。RNA测序显示，Add1缺失的成红细胞中p53通路被激活，导致在14体节期和受精后24小时出现细胞凋亡。有趣的是，Add1功能不足时可观察到贫血表型和细胞凋亡得到部分挽救。从机制上讲，发现ADD1可调节启动子活性。这些发现表明，Add1在斑马鱼红细胞生成中起关键作用，涉及p53介导的凋亡途径，从而将其调节作用扩展到细胞骨架功能之外。
