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Papers In Press, published online ahead of print June 18, 2004
Department of Biochemistry & Molecular Biology, University of Oklahoma College of Medicine, Oklahoma City, OK 73190
Corresponding Author: paul-weigel{at}ouhsc.edu
Human HARE mediates the clearance of hyaluronan (HA) and chondroitin sulfate (CS) from lymph and blood. Two hHARE isoforms (190 kDa and 315 kDa) are present in sinusoidal endothelial cells of liver, spleen and lymph nodes. Here we report the specificity and function of the 190 kDa HARE, expressed alone, in Flp-In 293 cell lines (190hHARE cells). Recombinant hHARE contains ~25 kDa of N-linked oligosaccharides, binds HA in a ligand blot assay, cross-reacts with three anti-rat HARE monoclonal antibodies, and is inactivated by reduction. 190hHARE cell lines mediated continuous 125I-HA endocytosis and degradation for hours. About 30-50% of the total cellular receptors were on the cell surface and their recycling time for reutilization was ~8.5 minutes. The average Kd for the binding of HA to the 190 kDa hHARE at 4oC was 7 nM with 118,000 total HA-binding sites/cell. Competition studies at 37oC indicated that the 190 kDa hHARE binds HA and chondroitin better than dermatan sulfate and chondroitin sulfates A, C, D, and E, but it does not bind to heparin, heparan sulfate, or keratan sulfate. Although competition was observed at 37oC, none of the glycosaminoglycans tested, except HA, competed for 125I-HA binding by 190hHARE cells at 4oC. Anti-HARE antibodies #30 and #154 partially blocked HA endocytosis by the 190 kDa hHARE. Thus, the 190 kDa hHARE can function independently of other hHARE isoforms to mediate the endocytosis of multiple glycosaminoglycans. Furthermore, the rat and human small HARE isoforms have different glycosaminoglycan specificities and antibody inhibition profiles.
J. Biol. Chem, 10.1074/jbc.M405322200
Submitted on May 12, 2004
Revised on June 18, 2004
Accepted on June 18, 2004
Endocytic function, glycosaminoglycan specificity, and antibody sensitivity of the recombinant human 190 kDa hare (hyaluronan receptor for endocytosis)
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