Endocytic Function, Glycosaminoglycan Specificity, and Antibody Sensitivity of the Recombinant Human 190-kDa Hyaluronan Receptor for Endocytosis (HARE)

Harris, Edward N.; Weigel, Janet A.; Weigel, Paul H.

doi:10.1074/jbc.m405322200

Cited by 77 publications

(138 citation statements)

References 43 publications

Supporting

Mentioning

130

Contrasting

Unclassified

Order By: Relevance

“…The 190-HARE is identical to the C-terminal 1417 amino acids of the full-length HARE (Fig. 1A), which we previously suggested arises by proteolytic cleavage (29,37).…”

Section: Two Isoforms Of Hare Are Expressed From a Singlesupporting

confidence: 75%

“…This full-length HARE DNA sequence obtained was identical to that of NCBI accession entry NM_017564 with the exception of silent mutations located at codons 833,1112,1700,1937,2005, and 2175 and one missense mutation, which created a D1276A mutation. However, Ala 1276 was reported in an earlier entry for stabilin-2 (accession number AJ295695) and was also present in the 190 hHARE clones reported by Harris et al (37). The D1276A change does not appear to affect the biological activity of the receptor and probably represents a polymorphism in the human STAB2 gene.…”

Section: Methodsmentioning

confidence: 75%

“…Thus, the levels of each isoform appear highly regulated (30,33), but it is still not known why or how this occurs. We recently confirmed that the 190-kDa hHARE is, in fact, a functional endocytic recycling receptor that can mediate GAG uptake in the absence of the larger 315-kDa hHARE (37).…”

mentioning

confidence: 61%

“…Endocytosis and Degradation of 125 I-HA-The C-terminal epitope tags do not interfere with HA binding, internalization, or trafficking mediated by the 190-kDa HARE (37). Stably transfected cell lines expressing the 315-HARE were plated in 12-well dishes and allowed to grow in DMEM with 8% fetal calf serum supplemented with 100 g/ml hygromycin B at least 2 days prior to an experiment.…”

Section: Methodsmentioning

confidence: 99%

“…A primary function of this receptor is to bind and internalize HA for turnover, although other GAGs, such as the CSs (20, 34 -37) (this report) are also internalized by this receptor, and advanced glycation end products appear to be ligands as well (38,39). The internalized receptor traffics through the early endocytic pathway and is recycled to the cell surface (21,29,37,39). A 20-min recycling time was observed for the rat 175-kDa HARE expressed in SK-Hep1 cell lines, whereas a 7-9-min cycle rate was observed with the 190-kDa hHARE expressed in Flp-In 293 cells.…”

mentioning

confidence: 88%

See 4 more Smart Citations

Expression, Processing, and Glycosaminoglycan Binding Activity of the Recombinant Human 315-kDa Hyaluronic Acid Receptor for Endocytosis (HARE)

Harris

Kyosseva

Weigel

et al. 2007

Journal of Biological Chemistry

Self Cite

120

156

View full text Add to dashboard Cite

The hyaluronic acid (HA) receptor for endocytosis (HARE; also designated stabilin-2 and FEEL-2) mediates systemic clearance of glycosaminoglycans from the circulatory and lymphatic systems via coated pit-mediated uptake. HARE is primarily found as two isoforms ( The glycosaminoglycan (GAG)2 hyaluronic acid (HA) is a protein-free polymer of disaccharide units containing glucuronic acid and N-acetylglucosamine (1, 2). HA is involved in many physiological processes (3), such as wound healing, development, and metastasis of some cancers (4 -8). The typical molecular mass of the polysaccharide ranges from just a few thousand Da (tens of sugars) that are thought to be important in cellular signaling (6) to several million Da (tens of thousands of sugars). These larger forms of HA are present throughout the body and are particularly concentrated within the bursa of major joints, such as the knee, where they help to provide shock absorbance in cartilage or lubrication in synovial fluid (9, 10), and the eye, where HA maintains structural integrity of the vitreous humor (11). The adult human body contains ϳ15 g of HA, of which about 5 g are turned over daily (12). Partially degraded HA perfuses from extracellular matrices (ECMs) and enters the lymphatic and vascular circulation systems, where it is catabolized to shorter fragments. This active maintenance of HA turnover must be efficient in order to maintain homeostatic conditions for total body HA.All of the other GAGs, including the chondroitin sulfates (CSs), heparan sulfate (HS), and keratan sulfate, are linked to core proteins (as proteoglycans) that help to form ECMs, such as the basement membranes of tissues, or structural components of organs, such as the vitreous humor. There are over 30 known core proteins that are essential for a diverse array of functions, such as neural development, growth factor signaling, and pathogen recognition (13). These core proteins are found as prevalent components of tissue ECMs or as specialized components needed for the development of microenvironments that interface a specialized tissue cell type with the ECM. Both the proteoglycans and their attached GAG chains may combinatorially interact with ligands and contribute to modulation of the functional aspects of a particular microenvironment (e.g. CS interacting with apolipoprotein E for uptake of ␤-very low density lipoprotein in hippocampal neurons) (14). Although numerous studies have focused on how the inhibition of some CS proteoglycans enhances neural development, especially in injured spinal cord models, there is very little information on how CS and HS are catabolized. The current model is that extracellular chondroitinases, heparinases, and proteases initially break down these GAGs and proteoglycans, and their final digestion can then take place intracellularly at the local tissue * This research was supported by NIGMS, National Institutes of Health, Grant GM69961. The costs of publication of this article were defrayed in part by the payment of page charges. This article ...

show abstract

“…The 190-HARE is identical to the C-terminal 1417 amino acids of the full-length HARE (Fig. 1A), which we previously suggested arises by proteolytic cleavage (29,37).…”

Section: Two Isoforms Of Hare Are Expressed From a Singlesupporting

confidence: 75%

Section: Methodsmentioning

confidence: 75%

mentioning

confidence: 61%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 88%

See 3 more Smart Citations

Expression, Processing, and Glycosaminoglycan Binding Activity of the Recombinant Human 315-kDa Hyaluronic Acid Receptor for Endocytosis (HARE)

Harris

Kyosseva

Weigel

et al. 2007

Journal of Biological Chemistry

Self Cite

120

156

View full text Add to dashboard Cite

show abstract

Endogenous Polymers as Biomaterials for Nanoparticulate Gene Therapy

Zorzi

Seijo

Sánchez

2015

Handbook of Polymers for Pharmaceutical Technologies

View full text Add to dashboard Cite

Revealing the unbinding mechanics of hyaluronan·receptor interactions on live cells

Garcia‐Monge,

Goodenough,

Cıvaş

et al. 2024

Proteoglycan Research

View full text Add to dashboard Cite

The extracellular matrix polysaccharide hyaluronan (HA) and its receptors are important mediators of cell adhesion and migration, and tissue mechanics. While mechanical forces are clearly important in these processes, there is a lack of methods to study the effect of mechanical forces on individual bonds of HA with its receptors directly on the surface of cells. Here, we present an assay based on atomic force microscopy to probe the frequency of bond formation (along with the receptor surface density) and the mechanical resistance of HA·receptor bonds to a force ramp on live cells. We demonstrate the method using a lymphoma cell line with stably transfected CD44 and one‐end anchored HA chains. We validate that HA·CD44 unbinding forces on cells are high compared to their relatively low binding affinity, and that bond rupture is dominated by a single energy barrier. The new live cell single HA chain force spectroscopy assay can be used to reveal the interaction mechanics with CD44 or other receptors in distinct interaction geometries, and adapted for other glycosaminoglycans and their receptors.

show abstract

Endocytic Function, Glycosaminoglycan Specificity, and Antibody Sensitivity of the Recombinant Human 190-kDa Hyaluronan Receptor for Endocytosis (HARE)

Cited by 77 publications

References 43 publications

Expression, Processing, and Glycosaminoglycan Binding Activity of the Recombinant Human 315-kDa Hyaluronic Acid Receptor for Endocytosis (HARE)

Expression, Processing, and Glycosaminoglycan Binding Activity of the Recombinant Human 315-kDa Hyaluronic Acid Receptor for Endocytosis (HARE)

Endogenous Polymers as Biomaterials for Nanoparticulate Gene Therapy

Revealing the unbinding mechanics of hyaluronan·receptor interactions on live cells

Contact Info

Product

Resources

About