Evolutionary conservation and divergence of CXCL17 orthologs: functional evidence in reptiles and loss in the avian lineage.

Authors

Jie Yu, Hao-Zheng Li, Juan-Juan Wang, Ya-Li Liu, Zhan-Yun Guo

Published in

Archives of biochemistry and biophysics. Pages 111016. Oct 05, 2026. Epub Oct 05, 2026.

Abstract

The mucosal chemoattractant C-X-C motif chemokine ligand 17 (CXCL17) was recently identified as a ligand for the orphan G protein-coupled receptor 25 (GPR25). Although our recent studies have identified non-mammalian CXCL17 orthologs in fishes and amphibians, their presence in reptiles and birds remains unclear. In this study, we employed bioinformatic searches based on gene synteny and sequence features to identify reptilian and avian CXCL17s in public databases. We identified intact CXCL17s in 46 reptilian species. In contrast, we identified only CXCL17 gene relics in 22 bird species and found that some bird species also lost GPR25 gene, suggesting the avian lineage lost CXCL17-GPR25 signaling pair during evolution. A recombinant reptilian CXCL17 from Caretta caretta, termed Cc-CXCL17, directly bound to and efficiently activated its corresponding receptor, Cc-GPR25, in a C-terminal fragment-dependent manner. Activation of Cc-GPR25 by Cc-CXCL17 induced chemotactic movement of transfected human embryonic kidney (HEK) 293T cells. In cross-species activity assays, CXCL17s from other species had almost no activity towards Cc-GPR25; Cc-CXCL17 and human CXCL17 had low activity towards mallard GPR25, but all tested CXCL17s had no detectable activity towards chicken GPR25. However, chicken GPR25 could be activated by synthetic apelin and apela at high concentrations. Together with its gene synteny and sequence homology, chicken GPR25 seemed a partially active paralog of the chicken apelin receptor. Our findings demonstrate the presence of CXCL17 orthologs in extant reptiles and provide evidence for their evolutionary loss in the avian lineage, offering new insights into the phylogenetic distribution of the CXCL17-GPR25 signaling system.

PMID:
42833530
Bibliographic data and abstract were imported from PubMed on 06 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.