Tripartite-motif family protein 35-28 regulates microglia development by preventing necrotic death of microglial precursors in zebrafish
Tripartite-motif family protein 35-28 regulates microglia development by preventing necrotic death of microglial precursors in zebrafish
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三联基序家族蛋白 35-28 通过防止斑马鱼小胶质细胞前体坏死来调节小胶质细胞发育
DOI：
10.1074/jbc.ra119.012043
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发表时间：
2020-05
影响因子：
4.8
通讯作者：
Wen Zilong
中科院分区：
文献类型：
--
作者：
Yu Tao;Kuang Haoyue;Chen Jiahao;Lin Xi;Wu Yi;Chen Keyu;Zhang Mingjie;Zhang Wenqing;Wen Zilong
小胶质细胞是中枢神经系统（CNS）中的组织驻留巨噬细胞，在调节中枢神经系统发育和内稳态方面发挥着关键作用。然而，调控小胶质细胞发育的基因网络仍未完全明确。在此，我们……
Microglia are tissue-resident macrophages in the central nervous system (CNS) that play essential roles in the regulation of CNS development and homeostasis. Yet, the genetic networks governing microglia development remain incompletely defined. Here, we report the identification and characterization of a microglia-defective zebrafish mutant wulonghkz12 (wulhkz12) isolated from an ethylnitrosourea (ENU)-based genetic screen. We show that wulhkz12 mutants harbors a missense point mutation in the gene region encoding the PRY/SPRY domain of the tripartite-motif family protein 35-28 (trim35-28) gene. Time-lapse imaging revealed that the loss of Trim35-28 function causes lytic necrosis of microglial precursors/peripheral macrophages, as indicated by cytoplasmic swelling and membrane rupture of these precursors and accompanied by neutrophil infiltration and systemic inflammation. Intriguingly, the lytic necrosis of microglial precursors in trim35-28–deficient mutants appeared to depend neither on the canonical pyroptotic nor necroptotic pathways, as inhibition of the key component in each pathway could not rescue the microglia phenotype in trim35-28–deficient mutants. Finally, results from tissue-specific rescue experiments suggested that Trim35-28 acts cell-autonomously in the survival of microglial precursors. Taken together, the findings of our study reveal Trim35-28 as a regulatory protein essential for microglia development.
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影响因子：
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作者：
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10.1038/nri2413
发表时间：
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10.1177/1073858414530512
发表时间：
2015-04
期刊：
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影响因子：
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作者：
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通讯作者：
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