Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
J Innate Immun. 2011;3(5):519-29. doi: 10.1159/000327718. Epub 2011 Jun 17.
The formyl peptide receptor gene family encodes G protein-coupled receptors for phagocyte chemoattractants, including bacteria- and mitochondria-derived N-formylpeptides. The human family has 3 functional genes, whereas the mouse family has 7 functional genes and 2 possible pseudogenes (ΨFpr-rs2 and ΨFpr-rs3). Here we characterize ΨFpr-rs2, a duplication of Fpr-rs2. Compared to Fpr-rs2, the ΨFpr-rs2 ORF is 186 nucleotides shorter but 98% identical. Due to a deletion and frame shift, the sequences lack homology from amino acid 219-289. Both transcripts were detected constitutively in multiple immune organs; however, ΨFpr-rs2 was consistently less abundant than Fpr-rs2. LPS induced expression of ΨFpr-rs2, but not Fpr-rs2, in spleen and bone marrow. Both transcripts were detected constitutively in thioglycollate-elicited peritoneal neutrophils, whereas only Fpr-rs2 was detected in thioglycollate-elicited peritoneal macrophages. Both transcripts were induced in LPS-stimulated macrophages. ΨFpr-rs2-GFP fusion protein appeared in cytoplasm but not plasma membrane of transfected HEK 293 cells, whereas Fpr-rs2-GFP labeled only plasma membrane. Survival of ΨFpr-rs2(-/-) mice was 33% shorter than that of wild-type and heterozygous littermates (p < 0.05), but no signature pathology was identified. Since ΨFpr-rs2 is expressed in phagocytes and regulated by bacterial products, and may affect longevity, we propose renaming it Fpr-rs8, an atypical member of the formyl peptide receptor gene family.
甲酰肽受体基因家族编码吞噬细胞趋化因子的 G 蛋白偶联受体，包括细菌和线粒体衍生的 N-甲酰肽。人类家族有 3 个功能性基因，而小鼠家族有 7 个功能性基因和 2 个可能的假基因（ΨFpr-rs2 和 ΨFpr-rs3）。在这里，我们描述了 ΨFpr-rs2，它是 Fpr-rs2 的重复。与 Fpr-rs2 相比，ΨFpr-rs2 的 ORF 短 186 个核苷酸，但 98%相同。由于缺失和移码，该序列从氨基酸 219-289 处缺乏同源性。两种转录本在多个免疫器官中均持续表达；然而，ΨFpr-rs2 的丰度始终低于 Fpr-rs2。LPS 在脾和骨髓中诱导 ΨFpr-rs2 的表达，但不诱导 Fpr-rs2 的表达。两种转录本在硫代乙醇酸诱导的腹腔中性粒细胞中持续表达，而只有 Fpr-rs2 在硫代乙醇酸诱导的腹腔巨噬细胞中表达。两种转录本均在 LPS 刺激的巨噬细胞中诱导表达。转染的 HEK 293 细胞中，ΨFpr-rs2-GFP 融合蛋白出现在细胞质中而不是质膜中，而 Fpr-rs2-GFP 仅标记质膜。ΨFpr-rs2(-/-) 小鼠的存活率比野生型和杂合子同窝仔鼠短 33%（p < 0.05），但未发现特征性病理学改变。由于 ΨFpr-rs2 在吞噬细胞中表达并受细菌产物调节，并且可能影响寿命，因此我们建议将其重新命名为 Fpr-rs8，这是甲酰肽受体基因家族的一个非典型成员。
