Liu Li, Hu Wanbin, Kerman Fatima Didar, Spaink Herman P
Institute of Biology Leiden, Animal Science and Health, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Present address: Center for Thrombosis and Hemostasis (CTH), Johannes Gutenberg-University Medical Center, Langenbeckstraße 1, Bldg. 70855131 Mainz, Germany.
Int J Biol Sci. 2025 Jan 1;21(2):823-841. doi: 10.7150/ijbs.101055. eCollection 2025.
The TIRAP protein is an adaptor protein in TLR signaling which links TLR2 and TLR4 to the adaptor protein Myd88. The transcriptomic profiles of zebrafish larvae from a , and mutant and the corresponding wild type controls under unchallenged developmental conditions revealed a specific involvement of in calcium homeostasis and myosin regulation. Metabolomic profiling showed that the mutation results in lower glucose levels, whereas a mutation leads to higher glucose levels. A tail-wounding zebrafish larval model was used to identify the role of in leukocyte migration to tissue wounding. We found that more neutrophils were recruited to the wounded region in the mutant larvae compared to the wild type controls, whereas there was no difference in macrophage recruitment. In contrast, published data show that and mutants recruit fewer neutrophils and macrophages to the wounds. Based on cell tracking analysis, we demonstrate that the neutrophil migration speed is increased in the mutant in contrast to neutrophil behavior in and mutants. In conclusion, we show that plays specialized roles distinct from and in signaling, metabolic control, and in regulating neutrophil migration speed upon wounding.
TIRAP蛋白是Toll样受体（TLR）信号通路中的一种衔接蛋白，它将TLR2和TLR4与衔接蛋白髓样分化因子88（Myd88）相连。在未受刺激的发育条件下，对来自某突变体和相应野生型对照的斑马鱼幼体进行转录组分析，结果显示该突变体在钙稳态和肌球蛋白调节方面有特定作用。代谢组分析表明，该突变导致葡萄糖水平降低，而另一种突变则导致葡萄糖水平升高。利用尾损伤斑马鱼幼体模型来确定该突变体在白细胞向组织损伤部位迁移中的作用。我们发现，与野生型对照相比，该突变体幼体中有更多的中性粒细胞被招募到损伤区域，而巨噬细胞的招募没有差异。相比之下，已发表的数据表明，另两种突变体向伤口招募的中性粒细胞和巨噬细胞较少。基于细胞追踪分析，我们证明，与另两种突变体中的中性粒细胞行为相比，该突变体中中性粒细胞的迁移速度加快。总之，我们表明，该突变体在信号传导、代谢控制以及在损伤后调节中性粒细胞迁移速度方面发挥着与另两种突变体不同的特殊作用。
