Research ArticleCell Migration

Heparan sulfate differentially controls CXCL12α- and CXCL12γ-mediated cell migration through differential presentation to their receptor CXCR4

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Science Signaling  01 Nov 2016:
Vol. 9, Issue 452, pp. ra107
DOI: 10.1126/scisignal.aaf1839

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The playing field affects the players

Chemokines are small proteins that stimulate the directed migration of cells along a concentration gradient. In addition to binding to their G protein–coupled receptors, chemokines bind to heparan sulfate, a proteoglycan found in the extracellular matrix and on the surface of endothelial cells. Connell et al. found that although the γ isoform of the chemokine CXCL12 had a higher affinity for the receptor CXCR4 than did the α isoform, it was a poor stimulator of cellular migration. However, when CXCL12γ and heparan sulfate were presented together to cells, CXCR4 signaling was similar to that elicited by CXCL12α alone. Together, these data suggest that heparan sulfate acts to appropriately present some chemokines to their receptors rather than merely acting as a surface for their distribution. Thus, the design of drugs to target chemokine-receptor interactions should also take heparan sulfate binding into account.