Midkine binds specifically to sulfatide - The role of sulfatide in cell attachment midkine-coated surfaces

Midkine is a heparin-binding polypeptide which is implicated in the control of development and repair of various tissues. Recognition of sulfate group s in glycosaminoglycans is important for its function. To elucidate further its mechanism of action, the interactions of midkine with sulfated glycoli pids were studied. Of various glycolipids and lipids examined, midkine boun d strongly to sulfatide and cholesterol-3-sulfate (CHO-3-SO4) in a dose-dep endent manner but failed to bind to other standard glycolipids and lipids. The properties of midkine binding to sulfatide and to CHO-3-SO4 differed in their sensitivity to inhibition by anionic polysaccharides, salt concentra tion and unlabeled midkine. Heparin inhibited midkine binding to sulfatide but weakly inhibited its binding to CHO-3-SO4. Liposomes bearing sulfatide carried out significant interactions with immobilized midkine, whereas thos e bearing CHO-3-SO4 did not, incorporation of sulfatide into 32D cells and trypsinized COS cells enhanced I-125-labelled midkine binding, whereas inco rporation of ganglioside or galactosylceramide had no effect. Furthermore, sulfatide-incorporated cells enhanced cell attachment to midkine-coated cov erslips. These results indicate that midkine binds to sulfatide under physi ological conditions and the midkine-sulfatide interaction may be important in controlling cell attachment.