biostudies-literatureKim HTNational Research Foundation of Korea111https://www.ebi.ac.uk/biostudies/studies/S-EPMC11863771biostudies-literatureUnknown23(1)<h4>Background</h4>The trafficking of immune cells between lymphoid organs and circulation depends on gradients of CXCL12 and sphingosine-1-phosphate (S1P), mediated through their cognate receptors C-X-C chemokine receptor type 4 (CXCR4) and S1P receptor type 1 (S1P<sub>1</sub>). S1P<sub>1</sub> facilitates the egress of hematopoietic stem cells and lymphocytes by counteracting CXCR4-mediated retention signals. However, the molecular mechanisms underlying this interplay remain poorly understood. In this study, we uncover CXCR4-S1P<sub>1</sub> heteromerization and explore their functional interactions.<h4>Methods</h4>Bimolecular fluorescence complementation (BiFC) assay, proximity ligation assay (PLA), and quantitative bioluminescence resonance energy transfer (BRET) assay were employed to Cell communication and signaling : CCSRegulation of CXCR4 function by S1P&lt;sub&gt;1&lt;/sub&gt; through heteromerization.PMC118637712020R1A5A1018081Jeong JYHuh WKKim HTfalseRegulation of CXCR4 function by S1P&lt;sub&gt;1&lt;/sub&gt; through heteromerization.<h4>Background</h4>The trafficking of immune cells between lymphoid organs and circulation depends on gradients of CXCL12 and sphingosine-1-phosphate (S1P), mediated through their cognate receptors C-X-C chemokine receptor type 4 (CXCR4) and S1P receptor type 1 (S1P<sub>1</sub>). S1P<sub>1</sub> facilitates the egress of hematopoietic stem cells and lymphocytes by counteracting CXCR4-mediated retention signals. However, the molecular mechanisms underlying this interplay remain poorly understood. In this study, we uncover CXCR4-S1P<sub>1</sub> heteromerization and explore their functional interactions.<h4>Methods</h4>Bimolecular fluorescence complementation (BiFC) assay, proximity ligation assay (PLA), and quantitative bioluminescence resonance energy transfer (BRET) assay were employed to 2025-01-01T00:00:00Z2025 Feb2026-06-02T18:16:36.404Z2025-04-07T11:30:18.825ZS-EPMC118637714001203810.1186/s12964-025-02099-x