CXCR7, CXCR4 and CXCL12: an eccentric trio?
1Institute for Research in Biomedicine, CH-6500 Bellinzona, Switzerland. marcus.thelen@irb.unisi.ch
Journal of Neuroimmunology
|June 6, 2008
Summary
Chemokine receptor CXCR7 (also known as RDC1) binds CXCL11 and CXCL12 but does not mediate typical responses. It scavenges CXCL12, guiding CXCR4-dependent migration, and may play a subtle role in nervous tissue.
Area of Science:
- Immunology
- Neuroscience
- Molecular Biology
Background:
- CXCR7 (RDC1) is a G-protein coupled receptor binding inflammatory chemokines CXCL11 and CXCL12.
- Unlike typical chemokine receptors, CXCR7 does not mediate leukocyte trafficking.
- Its precise function remains under investigation, particularly in the nervous system.
Purpose of the Study:
- To elucidate the functional role of CXCR7 beyond typical chemokine receptor signaling.
- To investigate CXCR7's involvement in chemokine scavenging and its impact on cell migration.
- To explore potential signal transduction capabilities and its significance in neural tissues.
Main Methods:
- Ligand binding assays to confirm high-affinity chemokine interactions.
- Zebrafish studies to observe CXCR7's role in migration guidance.
- Analysis of CXCR7 knockout mouse models to assess neurological phenotypes.
- Exploration of potential signal transduction pathways.
Main Results:
- CXCR7 binds CXCL11 and CXCL12 with high affinity.
- CXCR7 functions in scavenging CXCL12, creating gradients for CXCR4-mediated migration in zebrafish.
- CXCR7 knockout mice show no apparent brain phenotype, suggesting a subtle role.
- Evidence suggests potential for CXCR7-mediated signal transduction, relevant to tumor biology.
Conclusions:
- CXCR7 acts as a CXCL12 scavenger, influencing directed cell migration.
- While not mediating typical chemokine responses, CXCR7 may possess signaling functions.
- Its pronounced expression in nervous tissue suggests a specialized, potentially subtle, role in neural function.
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