CXCR7 functions as a scavenger for CXCL12 and CXCL11

Naumann, Ulrike; Cameroni, Elisabetta; Pruenster, Monika; Mahabaleshwar, Harsha; Raz, Erez; Zerwes, Hans-Günter; Rot, Antal; Thelen, Marcus

doi:10.1371/journal.pone.0009175

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Journal article

CXCR7 functions as a scavenger for CXCL12 and CXCL11

Naumann, Ulrike Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Cameroni, Elisabetta Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Pruenster, Monika Walter-Brendel-Center for Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany
Mahabaleshwar, Harsha Institute of Cell Biology, University of Münster, Münster, Germany
Raz, Erez Institute of Cell Biology, University of Münster, Münster, Germany
Zerwes, Hans-Günter Novartis Institutes for Biomedical Research, Autoimmunity, Transplantation and Inflammation, Basel, Switzerland
Rot, Antal Medical Research Council, Center for Immune Regulation, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom
Thelen, Marcus Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland

11.02.2010

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Plos one. - 2010, vol. 5, no. 2, p. e9175

English Background: CXCR7 (RDC1), the recently discovered second receptor for CXCL12, is phylogenetically closely related to chemokine receptors, but fails to couple to G-proteins and to induce typical chemokine receptor mediated cellular responses. The function of CXCR7 is controversial. Some studies suggest a signaling activity in mammalian cells and zebrafish embryos, while others indicate a decoy activity in fish. Here we investigated the two propositions in human tissues. Methodology/Principal Findings: We provide evidence and mechanistic insight that CXCR7 acts as specific scavenger for CXCL12 and CXCL11 mediating effective ligand internalization and targeting of the chemokine cargo for degradation. Consistently, CXCR7 continuously cycles between the plasma membrane and intracellular compartments in the absence and presence of ligand, both in mammalian cells and in zebrafish. In accordance with the proposed activity as a scavenger receptor CXCR7-dependent chemokine degradation does not become saturated with increasing ligand concentrations. Active CXCL12 sequestration by CXCR7 is demonstrated in adult mouse heart valves and human umbilical vein endothelium. Conclusions/Significance: The finding that CXCR7 specifically scavenges CXCL12 suggests a critical function of the receptor in modulating the activity of the ubiquitously expressed CXCR4 in development and tumor formation. Scavenger activity of CXCR7 might also be important for the fine tuning of the mobility of hematopoietic cells in the bone marrow and lymphoid organs.

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