PMID- 32398256 OWN - NLM STAT- MEDLINE DCOM- 20210113 LR - 20210627 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 295 IP - 26 DP - 2020 Jun 26 TI - Tripartite-motif family protein 35-28 regulates microglia development by preventing necrotic death of microglial precursors in zebrafish. PG - 8846-8856 LID - S0021-9258(17)49378-1 [pii] LID - 10.1074/jbc.RA119.012043 [doi] AB - 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 wulong(hkz12) (wul(hkz12) ) isolated from an ethylnitrosourea (ENU)-based genetic screen. We show that wul(hkz12) 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. CI - (c) 2020 Yu et al. FAU - Yu, Tao AU - Yu T AD - Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University- The Hong Kong University of Science and Technology Medical Center, Shenzhen, China. FAU - Kuang, Haoyue AU - Kuang H AD - Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University- The Hong Kong University of Science and Technology Medical Center, Shenzhen, China. FAU - Chen, Jiahao AU - Chen J AD - Department of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangdong, Guangzhou, China. FAU - Lin, Xi AU - Lin X AD - Division of Life Science, State Key Laboratory of Molecular Neuroscience, Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China. FAU - Wu, Yi AU - Wu Y AD - Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University- The Hong Kong University of Science and Technology Medical Center, Shenzhen, China. FAU - Chen, Keyu AU - Chen K AD - Division of Life Science, State Key Laboratory of Molecular Neuroscience, Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Greater Bay Biomedical Innocenter, Shenzhen Bay Laboratory, Shenzhen, China. FAU - Zhang, Mingjie AU - Zhang M AD - Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University- The Hong Kong University of Science and Technology Medical Center, Shenzhen, China; Division of Life Science, State Key Laboratory of Molecular Neuroscience, Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Greater Bay Biomedical Innocenter, Shenzhen Bay Laboratory, Shenzhen, China. FAU - Zhang, Wenqing AU - Zhang W AD - Department of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangdong, Guangzhou, China. Electronic address: mczhangwq@scut.edu.cn. FAU - Wen, Zilong AU - Wen Z AD - Shenzhen Key Laboratory for Neuronal Structural Biology, Biomedical Research Institute, Shenzhen Peking University- The Hong Kong University of Science and Technology Medical Center, Shenzhen, China; Division of Life Science, State Key Laboratory of Molecular Neuroscience, Center of Systems Biology and Human Health, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Greater Bay Biomedical Innocenter, Shenzhen Bay Laboratory, Shenzhen, China. Electronic address: zilong@ust.hk. LA - eng SI - PDB/2wl1 PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20200512 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R SB - IM MH - Animals MH - Microglia/*cytology/physiology MH - Mutation, Missense MH - Necroptosis MH - Neural Stem Cells/*cytology/metabolism MH - Neurogenesis MH - Zebrafish/*embryology/genetics PMC - PMC7324517 OTO - NOTNLM OT - Trim OT - cell death OT - central nervous system (CNS,) OT - development OT - genetic screen OT - immune system OT - macrophage OT - microglia OT - neuronal inflammation OT - zebrafish COIS- Conflict of interest-The authors declare that they have no conflicts of interest with the contents of this article. EDAT- 2020/05/14 06:00 MHDA- 2021/01/14 06:00 PMCR- 2021/06/26 CRDT- 2020/05/14 06:00 PHST- 2019/11/25 00:00 [received] PHST- 2020/05/04 00:00 [revised] PHST- 2020/05/14 06:00 [pubmed] PHST- 2021/01/14 06:00 [medline] PHST- 2020/05/14 06:00 [entrez] PHST- 2021/06/26 00:00 [pmc-release] AID - S0021-9258(17)49378-1 [pii] AID - RA119.012043 [pii] AID - 10.1074/jbc.RA119.012043 [doi] PST - ppublish SO - J Biol Chem. 2020 Jun 26;295(26):8846-8856. doi: 10.1074/jbc.RA119.012043. Epub 2020 May 12.