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First published online 12 May 2009
doi: 10.1242/jcs.039057

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VASP is a CXCR2-interacting protein that regulates CXCR2-mediated polarization and chemotaxis

¹ Department of Veterans Affairs, Nashville, TN 37212, USA
² Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
³ Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
⁴ Mass Spectrometry Research Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
⁵ Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA

^* Author for correspondence (e-mail: ann.richmond{at}vanderbilt.edu)

Accepted 24 February 2009

Chemotaxis regulates the recruitment of leukocytes, which is integral for a number of biological processes and is mediated through the interaction of chemokines with seven transmembrane G-protein-coupled receptors. Several studies have indicated that chemotactic signaling pathways might be activated via G-protein-independent mechanisms, perhaps through novel receptor-interacting proteins. CXCR2 is a major chemokine receptor expressed on neutrophils. We used a proteomics approach to identify unique ligand-dependent CXCR2-interacting proteins in differentiated neutrophil-like HL-60 cells. Using this approach, vasodilator-stimulated phosphoprotein (VASP) was identified as a CXCR2-interacting protein. The interaction between CXCR2 and VASP is direct and enhanced by CXCL8 stimulation, which triggers VASP phosphorylation via PKA- and PKC-mediated pathways. The interaction between CXCR2 and VASP requires free F-actin barbed ends to recruit VASP to the leading edge. Finally, knockdown of VASP in HL-60 cells results in severely impaired CXCR2-mediated chemotaxis and polarization. These data provide the first demonstration that direct interaction of VASP with CXCR2 is essential for proper CXCR2 function and demonstrate a crucial role for VASP in mediating chemotaxis in leukocytes.

Key words: CXCR2, VASP, Chemotaxis, Actin, Phosphorylation

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