A functional heteromeric MIF receptor formed by CD74 and CXCR4

Schwartz, Verena; Lue, Hongqi; Kraemer, Sandra; Korbiel, Joanna; Krohn, Regina; Ohl, Kim; Bucala, Richard; Weber, Christian; Bernhagen, Jürgen

doi:10.1016/j.febslet.2009.07.058

« Previous Next »FEBS Letters
Volume 583, Issue 17 , Pages 2749-2757, 3 September 2009

A functional heteromeric MIF receptor formed by CD74 and CXCR4

Edited by Masayuki Miyasaka

Verena Schwartz
- Department of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany
- These authors contributed equally to this work.
Hongqi Lue
- Department of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany
- These authors contributed equally to this work.
Sandra Kraemer
- Department of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany
Joanna Korbiel
- Department of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany
Regina Krohn
- Institute of Molecular Cardiovascular Research, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany
Kim Ohl
- Department of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany
Richard Bucala
- Yale University School of Medicine, New Haven, CT 06520, USA
Christian Weber
- Institute of Molecular Cardiovascular Research, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany
Jürgen Bernhagen
- Department of Biochemistry and Molecular Cell Biology, RWTH Aachen University, Pauwelsstrasse 30, D-52074 Aachen, Germany
- Corresponding author.

Received 17 April 2009; received in revised form 26 July 2009; accepted 30 July 2009. published online 06 August 2009.

Abstract

MIF is a chemokine-like inflammatory mediator that triggers leukocyte recruitment by binding to CXCR2 and CXCR4. MIF also interacts with CD74/invariant chain, a single-pass membrane-receptor. We identified complexes between CD74 and CXCR2 with a role in leukocyte recruitment. It is unknown whether CD74 also binds to CXCR4. We demonstrate that CD74/CXCR4 complexes formed when CD74 was expressed with CXCR4 in HEK293 cells. Expression of CD74-variants lacking an ER-retention signal showed CD74/CXCR4 complexes at the cell surface. Importantly, endogenous CD74/CXCR4 complexes were isolated by co-immunoprecipitation from monocytes. Finally, MIF-stimulated CD74-dependent AKT activation was blocked by anti-CXCR4 and anti-CD74 antibodies and AMD3100, whereas CXCL12-stimulated AKT activation was not reduced by anti-CD74. Thus, CD74 forms functional complexes with CXCR4 that mediate MIF-specific signaling.

Structured summary

MINT-7234512, MINT-7234528: CD74 (uniprotkb:P04233) physically interacts (MI:0915) with CXCR4 (uniprotkb:P61073) by anti tag coimmunoprecipitation (MI:0007)

MINT-7234542: CD74 (uniprotkb:P04233) and CXCR4 (uniprotkb:P61073) physically interact (MI:0915) by anti bait coimmunoprecipitation (MI:0006)

MINT-7234499: CXCR4 (uniprotkb:P61073) and CD74 (uniprotkb:P04233) colocalize (MI:0403) by fluorescence microscopy (MI:0416)

Abbreviations: CoIP, coimmunoprecipitation, CXCR, CXC-type chemokine receptor, CXCL, CXC-type chemokine ligand, GPCR, G protein-coupled receptor, Ii, invariant chain, MIF, macrophage migration inhibitory factor, SDF-1α, stromal cell-derived factor-1α