GPR15LG与CXCR4结合，并协同调节CXCL12诱导的细胞信号传导和迁移。

GPR15LG binds CXCR4 and synergistically modulates CXCL12-induced cell signaling and migration.

作者信息

Albers Dan Pascal Jean, Novikova Sofya, Vieyto-Nuñez Julio, Almeida-Hernández Yasser, Pastorio Chiara, Klassen Florian, Weiss Dana, von Maltitz Pascal, Jaikishan Janeni, Datta Moumita, Jumaa Hassan, Jebaraj Billy Michael Chelliah, Stilgenbauer Stephan, Kumar Manish, Maity Palash Chandra, Buske Christian, Stifel Ulrich, Zinngrebe Julia, Fischer-Posovszky Pamela, Chevigné Andy, Kirchhoff Frank, Sanchez-Garcia Elsa, Münch Jan, Harms Mirja

机构信息

Institute of Molecular Virology, Ulm University Medical Center, 89081, Ulm, Germany.

Chair of Computational Bioengineering, Department of Biochemical and Chemical Engineering, Technical University Dortmund, 44227, Dortmund, Germany.

出版信息

Cell Commun Signal. 2025 May 20;23(1):234. doi: 10.1186/s12964-025-02231-x.

DOI:10.1186/s12964-025-02231-x

PMID:40394646

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12093852/

Abstract

BACKGROUND

GPR15LG, a chemokine-like ligand for the G-protein coupled receptor 15 (GPR15), is abundantly expressed in the gastrointestinal mucosa and inflamed skin. Emerging evidence suggests its involvement in inflammatory disorders and cancers. C-X-C chemokine receptor type 4 (CXCR4) plays a critical role in immune cell trafficking and cancer metastasis. Recent evidence suggests a connection between GPR15LG and CXCR4 signaling, which has not been investigated so far.

METHODS

We investigated the effects of GPR15LG on CXCR4 signaling and downstream functions. Binding assays and computational modeling were performed to assess the interaction between GPR15LG and CXCR4. Functional assays, including wound healing and cell migration assays, were conducted across various cell types, including CD4⁺ T cells and cancer cells, to evaluate the impact of GPR15LG on CXCL12-mediated CXCR4 signaling.

RESULTS

The results demonstrate that GPR15LG binds to the orthosteric site of CXCR4, modulating downstream signaling in a context-dependent manner. Specifically, GPR15LG enhances CXCL12-mediated CXCR4 signaling synergistically, promoting wound healing and cell migration across various cell types, including CD4 + T cells and cancer cells.

CONCLUSIONS

These findings underscore the role of GPR15LG in inflammation and metastasis, offering potential therapeutic avenues for CXCR4-mediated diseases.

摘要

背景

GPR15LG是G蛋白偶联受体15（GPR15）的一种趋化因子样配体，在胃肠道黏膜和炎症皮肤中大量表达。新出现的证据表明其参与炎症性疾病和癌症。C-X-C趋化因子受体4型（CXCR4）在免疫细胞运输和癌症转移中起关键作用。最近的证据表明GPR15LG与CXCR4信号传导之间存在联系，而这一点迄今尚未得到研究。