GPR15LG binds CXCR4 and synergistically modulates CXCL12-induced cell signaling and migration
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) play...
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BMC
2025-05-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | https://doi.org/10.1186/s12964-025-02231-x |
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| author | Dan Pascal Jean Albers Sofya Novikova Julio Vieyto-Nuñez Yasser Almeida-Hernández Chiara Pastorio Florian Klassen Dana Weiss Pascal von Maltitz Janeni Jaikishan Moumita Datta Hassan Jumaa Billy Michael Chelliah Jebaraj Stephan Stilgenbauer Manish Kumar Palash Chandra Maity Christian Buske Ulrich Stifel Julia Zinngrebe Pamela Fischer-Posovszky Andy Chevigné Frank Kirchhoff Elsa Sanchez-Garcia Jan Münch Mirja Harms |
| author_facet | Dan Pascal Jean Albers Sofya Novikova Julio Vieyto-Nuñez Yasser Almeida-Hernández Chiara Pastorio Florian Klassen Dana Weiss Pascal von Maltitz Janeni Jaikishan Moumita Datta Hassan Jumaa Billy Michael Chelliah Jebaraj Stephan Stilgenbauer Manish Kumar Palash Chandra Maity Christian Buske Ulrich Stifel Julia Zinngrebe Pamela Fischer-Posovszky Andy Chevigné Frank Kirchhoff Elsa Sanchez-Garcia Jan Münch Mirja Harms |
| author_sort | Dan Pascal Jean Albers |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b4d63360e89b4b1cb7d298f5018a68bf |
| institution | Kabale University |
| issn | 1478-811X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj-art-b4d63360e89b4b1cb7d298f5018a68bf2025-08-20T04:02:54ZengBMCCell Communication and Signaling1478-811X2025-05-0123112010.1186/s12964-025-02231-xGPR15LG binds CXCR4 and synergistically modulates CXCL12-induced cell signaling and migrationDan Pascal Jean Albers0Sofya Novikova1Julio Vieyto-Nuñez2Yasser Almeida-Hernández3Chiara Pastorio4Florian Klassen5Dana Weiss6Pascal von Maltitz7Janeni Jaikishan8Moumita Datta9Hassan Jumaa10Billy Michael Chelliah Jebaraj11Stephan Stilgenbauer12Manish Kumar13Palash Chandra Maity14Christian Buske15Ulrich Stifel16Julia Zinngrebe17Pamela Fischer-Posovszky18Andy Chevigné19Frank Kirchhoff20Elsa Sanchez-Garcia21Jan Münch22Mirja Harms23Institute of Molecular Virology, Ulm University Medical CenterInstitute of Molecular Virology, Ulm University Medical CenterChair of Computational Bioengineering, Department of Biochemical and Chemical Engineering, Technical University DortmundChair of Computational Bioengineering, Department of Biochemical and Chemical Engineering, Technical University DortmundInstitute of Molecular Virology, Ulm University Medical CenterInstitute of Molecular Virology, Ulm University Medical CenterInstitute of Molecular Virology, Ulm University Medical CenterInstitute of Molecular Virology, Ulm University Medical CenterInstitute of Immunology, Ulm University Medical CenterInstitute of Immunology, Ulm University Medical CenterInstitute of Immunology, Ulm University Medical CenterDivision of CLL, Department of Internal Medicine III, Ulm University Medical CenterDivision of CLL, Department of Internal Medicine III, Ulm University Medical CenterInstitute of Experimental Cancer Research, Ulm University Medical CenterInstitute of Experimental Cancer Research, Ulm University Medical CenterInstitute of Experimental Cancer Research, Ulm University Medical CenterDepartment of Pediatrics and Adolescent Medicine, University Medical CenterDepartment of Pediatrics and Adolescent Medicine, University Medical CenterDepartment of Pediatrics and Adolescent Medicine, University Medical CenterImmuno-Pharmacology and Interactomics, Department of Infection and Immunity, Luxembourg Institute of Health (LIH)Institute of Molecular Virology, Ulm University Medical CenterChair of Computational Bioengineering, Department of Biochemical and Chemical Engineering, Technical University DortmundInstitute of Molecular Virology, Ulm University Medical CenterInstitute of Molecular Virology, Ulm University Medical CenterAbstract 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.https://doi.org/10.1186/s12964-025-02231-xGPR15LGCXCR4 signalingImmune cell migrationCancer metastasisWound healing |
| spellingShingle | Dan Pascal Jean Albers Sofya Novikova Julio Vieyto-Nuñez Yasser Almeida-Hernández Chiara Pastorio Florian Klassen Dana Weiss Pascal von Maltitz Janeni Jaikishan Moumita Datta Hassan Jumaa Billy Michael Chelliah Jebaraj Stephan Stilgenbauer Manish Kumar Palash Chandra Maity Christian Buske Ulrich Stifel Julia Zinngrebe Pamela Fischer-Posovszky Andy Chevigné Frank Kirchhoff Elsa Sanchez-Garcia Jan Münch Mirja Harms GPR15LG binds CXCR4 and synergistically modulates CXCL12-induced cell signaling and migration Cell Communication and Signaling GPR15LG CXCR4 signaling Immune cell migration Cancer metastasis Wound healing |
| title | GPR15LG binds CXCR4 and synergistically modulates CXCL12-induced cell signaling and migration |
| title_full | GPR15LG binds CXCR4 and synergistically modulates CXCL12-induced cell signaling and migration |
| title_fullStr | GPR15LG binds CXCR4 and synergistically modulates CXCL12-induced cell signaling and migration |
| title_full_unstemmed | GPR15LG binds CXCR4 and synergistically modulates CXCL12-induced cell signaling and migration |
| title_short | GPR15LG binds CXCR4 and synergistically modulates CXCL12-induced cell signaling and migration |
| title_sort | gpr15lg binds cxcr4 and synergistically modulates cxcl12 induced cell signaling and migration |
| topic | GPR15LG CXCR4 signaling Immune cell migration Cancer metastasis Wound healing |
| url | https://doi.org/10.1186/s12964-025-02231-x |
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