Receptor-mediated uptake of HA

Stable Identifier
Reaction [binding]
Homo sapiens
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HA receptors mediate the uptake of HA into cells. CD44 consists of four functional domains, the extracellular distal domain being the HA-binding region (Culty et al. 1990, Asher & Bignami 1992). The receptor for hyaluronan mediated motility (RHAMM, also called HMMR) can bind HA but not heparin or chondroitin sulfate (Assmann et al. 1998, Wang et al. 1996). Lymphatic vessel endothelial hyaluronic acid receptor 1 (LYVE1) removes HA from the lymphatic system (Banerji et al. 1999). It is present mainly on lymphatic endothelial cells but also in liver sinusoids. Hyaluronan receptor for endocytosis (HARE, stabilin-2, STAB2) binds to and mediates endocytosis of HA (Harris et al. 2007, Harris et al. 2004). HARE can also bind other glycosaminoglycans such as heparin (Harris et al. 2008).
High molecular weight HA is tethered to the cell surface by HA receptors and the GPI-linked hyaluronidase 2 (HYAL2) to form a HA:HAR:HYAL2 complex in the plasma membrane that localizes to caveolae (invaginations of the plasma membrane composed of cholesterol and gangliosides and rich in caveolin and flotillin).
Literature References
PubMed ID Title Journal Year
1426053 Hyaluronate binding and CD44 expression in human glioblastoma cells and astrocytes

Bignami, A, Asher, R

Exp Cell Res 1992
1703543 The hyaluronate receptor is a member of the CD44 (H-CAM) family of cell surface glycoproteins

Miyake, K, Underhill, C, Kincade, PW, Butcher, EC, Sikorski, E, Culty, M

J Cell Biol 1990
8890751 The characterization of a human RHAMM cDNA: conservation of the hyaluronan-binding domains

Li, Q, Turley, EA, Hou, G, Entwistle, J, Wang, C

Gene 1996
18434317 The human hyaluronan receptor for endocytosis (HARE/Stabilin-2) is a systemic clearance receptor for heparin

Weigel, PH, Weigel, JA, Harris, EN

J Biol Chem 2008
9601098 The human hyaluronan receptor RHAMM is expressed as an intracellular protein in breast cancer cells

Assmann, V, Fieber, C, Hofmann, M, Marshall, JF, Hart, IR

J Cell Sci 1998
15208308 Endocytic function, glycosaminoglycan specificity, and antibody sensitivity of the recombinant human 190-kDa hyaluronan receptor for endocytosis (HARE)

Weigel, PH, Weigel, JA, Harris, EN

J Biol Chem 2004
10037799 LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan

Ni, J, Su, J, Banerji, S, Jackson, DG, Tammi, R, Clasper, S, Jones, M, Wang, SX

J Cell Biol 1999
17145755 Expression, processing, and glycosaminoglycan binding activity of the recombinant human 315-kDa hyaluronic acid receptor for endocytosis (HARE)

Kyosseva, SV, Weigel, PH, Weigel, JA, Harris, EN

J Biol Chem 2007
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