Reactome | Receptor-mediated uptake of HA

Receptor-mediated uptake of HA

Stable Identifier

R-HSA-2160915

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane, extracellular region

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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