cxcr7 functions as a scavenger for cxcl12 and cxcl11cxcr7函数作为cxcl12和cxcl11清道夫.pdfVIP

CXCR7 Functions as a Scavenger for CXCL12 and CXCL11 1 1 2 3 3 Ulrike Naumann , Elisabetta Cameroni , Monika Pruenster , Harsha Mahabaleshwar , Erez Raz , Hans- ¨ 4 5 1 Gunter Zerwes , Antal Rot , Marcus Thelen * 1 Institute for Research in Biomedicine, Bellinzona, Switzerland, 2 Walter-Brendel-Center for Experimental Medicine, Ludwig-Maximilians-University, Munich, Germany, ¨ ¨ 3 Institute of Cell Biology, University of Munster, Munster, Germany, 4 Novartis Institutes for Biomedical Research, Autoimmunity, Transplantation and Inflammation, Basel, Switzerland, 5 Medical Research Council, Center for Immune Regulation, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom Abstract 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 pres