Mater Research Institute-University of Queensland, Translational Research Institute, Woolloongabba, QLD 4102, Australia.
The Roslin Institute, University of Edinburgh, Midlothian, United Kingdom.
J Leukoc Biol. 2020 Feb;107(2):237-250. doi: 10.1002/JLB.6MA0519-172R. Epub 2019 Sep 5.
Macrophage colony-stimulating factor (CSF1 or M-CSF) and interleukin 34 (IL34) are secreted cytokines that control macrophage survival and differentiation. Both act through the CSF1 receptor (CSF1R), a type III transmembrane receptor tyrosine kinase. The functions of CSF1R and both ligands are conserved in birds. We have analyzed protein-coding sequence divergence among avian species. The intracellular tyrosine kinase domain of CSF1R was highly conserved in bird species as in mammals but the extracellular domain of avian CSF1R was more divergent in birds with multiple positively selected amino acids. Based upon crystal structures of the mammalian CSF1/IL34 receptor-ligand interfaces and structure-based alignments, we identified amino acids involved in avian receptor-ligand interactions. The contact amino acids in both CSF1 and CSF1R diverged among avian species. Ligand-binding domain swaps between chicken and zebra finch CSF1 confirmed the function of variants that confer species specificity on the interaction of CSF1 with CSF1R. Based upon genomic sequence analysis, we identified prevalent amino acid changes in the extracellular domain of CSF1R even within the chicken species that distinguished commercial broilers and layers and tropically adapted breeds. The rapid evolution in the extracellular domain of avian CSF1R suggests that at least in birds this ligand-receptor interaction is subjected to pathogen selection. We discuss this finding in the context of expression of CSF1R in antigen-sampling and antigen-presenting cells.
巨噬细胞集落刺激因子 (CSF1 或 M-CSF) 和白细胞介素 34 (IL34) 是控制巨噬细胞存活和分化的分泌细胞因子。两者都通过 CSF1 受体 (CSF1R) 起作用，CSF1R 是一种 III 型跨膜受体酪氨酸激酶。CSF1R 和两种配体的功能在鸟类中是保守的。我们分析了鸟类物种之间的蛋白质编码序列差异。CSF1R 的细胞内酪氨酸激酶结构域在鸟类和哺乳动物中高度保守，但鸟类 CSF1R 的细胞外结构域在具有多个正选择氨基酸的鸟类中更加多样化。基于哺乳动物 CSF1/IL34 受体-配体界面的晶体结构和基于结构的比对，我们确定了参与鸟类受体-配体相互作用的氨基酸。CSF1 和 CSF1R 中的接触氨基酸在鸟类中发生了分化。鸡和斑胸草雀 CSF1 之间的配体结合域交换证实了赋予 CSF1 与 CSF1R 相互作用物种特异性的变体的功能。基于基因组序列分析，我们甚至在鸡种中发现了 CSF1R 细胞外结构域中的常见氨基酸变化，这些变化区分了商业肉鸡和蛋鸡以及热带适应品种。鸟类 CSF1R 细胞外结构域的快速进化表明，至少在鸟类中，这种配体-受体相互作用受到病原体选择的影响。我们在 CSF1R 在抗原采样和抗原呈递细胞中的表达背景下讨论了这一发现。
