Biomechanical Properties of Hyaluronan

The ability of HA to form highly polarized chains in the ECM allows it to attract and regulate water content, which affects several biomechanical properties of the vocal fold. Vocal fold tissues have been described as viscoelastic, demonstrating both viscous and elastic properties. Viscosity and elasticity are essential to voice because they directly affect the initiation and maintenance of phonation (6,22) as well as the vocal fold fundamental frequency. It has been demonstrated theoretically...

Hyaluronan in Atherosclerosis

Atherosclerosis is a disease of medium and large-sized arteries that claims more lives in the western world than any other disease (12). The disease involves the progressive thickening of blood vessels over several decades of life due to accumulations of cells, components of the extracellular matrix (ECM) and deposits of lipids in the form of lipoproteins with the eventual formation of the atherosclerotic plaque. With time, the plaques weaken and rupture leading to thrombosis and occlusion...

Introduction

The pulmonary alveolus is the final result of the branching of the air passages in the lung. It is spherical, with a diameter of about 250 mm, in order to present the most surface for air exchange to occur. There are approximately 3 X 108 alveoli in the adult human lung and the total surface area they present is about 80 m2. In order for the path of oxygen and carbon dioxide to be as short as possible, each alveolus is in apposition to a blood capillary and the area of the alveolar-capillary...

C Rhamm is a Multifunctional Adapter Targeting Protein

Murine and human RHAMM genes do not contain significant sequence homology with any single gene from lower organisms for which extensive genomic sequence is available (e.g., Drosophila or C. elegans), and therefore is admittedly a difficult gene to assign to a family of proteins using standard criteria. Reviewing all of the established functional properties and binding associations of RHAMM, even if collectively these do not fit neatly into currently accepted classification paradigms, and...

Summary and Conclusion

HA levels are determined by relative rates of synthesis and degradation. Abnormal degradation rates can be observed in a variety of diseases (tumor, shock, cancer, etc.) or bacterial infections. Hyaluronidases may be secreted and later on, taken up to be delivered to lysosomes. These enzymes may also be involved in receptor-mediated endocytosis of the substrate. More work remains to be done to fully characterize the biological roles of both bacterial and mammalian-type HA degrading enzymes. The...

Summary and Conclusions

In summary, existing studies about the presence and function of HA in the ocular surface and its role as a therapeutic tool show 1. HA is found as a component of the normal ocular surface. Its presence was described in tears, lacrimal tissue, conjunctiva and cornea. 2. In the normal ocular surface, it has been demonstrated that the presence of the HA receptor CD44 is always closely associated with HA. HA plays a role in the regulation of corneal epithelial regeneration, promoting epithelial...

Hyaluronan in Adhesion Migration and Invasion of Cancer

CD44 and HA are involved in a variety of biological processes and CD44 is often up-regulated with HA at sites of inflammation (52) and tumour invasion (8). There are now extensive data to indicate that interaction of HA with CD44 and the RHAMM receptors are involved in tumour cell adhesion, migration, invasion, and tumour growth. Adhesion of tumour cells to stromal cells is an important step in tumour establishment and recently expression of CD44v9 on myeloma plasma cells, which is correlated...

Formation of the SHAPHyaluronan Complex A Isolation and Identification of SHAP

When cultured in dishes, fibroblasts form a hyaluronan-rich extracellular matrix in the surrounding pericellular space. From the matrix, hyaluronan was isolated together with a protein of 85 kDa even in the presence of 6 M guanidine hydrochloride and detergents, a condition known to disrupt most non-covalent interactions (19). The protein was derived from the serum added to the culture medium because it was not metabolically labeled, and thus was designated SHAP at that time. Then the partial...

Strategies to Reduce Postsurgical Adhesion Formation

There are essentially three ways to reduce adhesion formation 1 reduce tissue damage during a procedure 2 use a therapeutic that will affect fibrin resorbtion, such as a fibrinolytic or anti-inflammatory agent or 3 use a barrier that will keep tissue planes separated until the fibrin clot has been resorbed and normal wound healing has taken place. Adhesion formation can be influenced by surgical technique (54,62-64) and the use of surgical irrigants such as Ringer's Lactate (65), Sepracoat...

Synthesis and Metabolism of Epidermal Hyaluronan

The currently available data on hyaluronan metabolism in the epidermis is derived from metabolic labeling of pig (10) and human (1) skin explants in organ culture and organotypic, differentiating rat keratinocyte cultures (11). Analysis of 3H-glucosamine incorporation revealed that hyaluronan was the major glycosa-minoglycan synthesized in human epidermis (1,11). Furthermore, the heparan sulfate containing isoform of the hyaluronan receptor CD44 is one of the major proteoglycans in this tissue...

Hyaluronan in Restenosis

Hyaluronan Extracellular Matrix

Vessels that become blocked can be treated by removing the plaque by percutaneous transluminal angioplasty, which surgically splits or dissects the plaque to reopen the blood vessel (61). However, in a large percentage of these patients, the treated vessels reocclude in a remarkably short period of time (3-6 months), necessitating further surgery. This process of reocclusion is called restenosis and is thought to involve a combination of blood vessel thickening and tissue shrinkage (62). Data...

References

Influence of retinoic acid on the ultrastructure and hyaluronic acid synthesis of adult human epidermis in whole skin organ culture. J Cell Physiol 1986 126 389-398. 2. Tammi R, Ripellino JA, Margolis RU, Tammi M. Localization of epidermal hyaluronic acid using the hyaluronate binding region of cartilage proteoglycan as a specific probe. J Invest Dermatol 1988 90 412-414. 3. Tammi R, Agren UM, Tuhkanen AL, Tammi M. Hyaluronan metabolism in skin. Prog Histochem Cytochem 1994 29...

Hyaluronan in Epidermal Appendices and Other Derivatives of Ectodermal Epithelium

Stratified layers of keratinocytes constitute the epidermis, but a number of other epithelial cell types differentiate from the same primitive surface ectoderm during the early embryonic period. These cell types include the secretory and conducting channels of sweat glands, the several cells involved in hair formation, the sebaceous glands and sebocytes and the suggested stem cell population located in the hair bulge (21). The epithelial, secretory cells of tear glands, mammary glands and...

Hyaluronidase Mediated Degradation

Hyaluronidases are considered responsible for much of the HA catabolism taking place in the organisms (see Chapter 17 for details). Successful fertilization in mammals is dependent on the action of hyaluronidase, when the sperm traverses the outermost HA-rich cumulus layer surrounding the egg (32). Therefore, all mammalian spermatozoa bear hyaluronidase activity. A protein, first of all characterized with the aid of a monoclonal antibody against posterior head determinants and thus named PH-20...

Interaction of CD44 and the Actin Cytoskeleton and Lipid Rafts

When detergents such as Triton X-100 or NP-40 are used to extract CD44 from the plasma membrane a significant pool of CD44 remains, still associated with the residual membrane fraction (93,94). In order to solubilize the remaining CD44 on mouse 3T3 cells, Underhill et al. found that cytoskeleton-disrupting reagents such as phalloidin, cytochalasin B or DNase, in additional to detergent, were necessary (93). The NP-40 resistant pool found in resident macrophages (42 of the total CD44) was...

Conformation of Hyaluronan in Solution

Concentration Weight Naoh Nacl

With the premise that HA may self-associate, but the interactions may be weak and transient, we set out in our research group to investigate HA properties in concentrated solutions and look for evidence of self-association. For this study we used a newly developed technique, confocal-FRAP, which is uniquely suited for detecting weak associations and is able to study at high concentration, where chain-chain interaction could be expected to be maximal. This new technique could thus provide...

Gastrointestinal and Respiratory Epithelium

Avidine Biotine Peroxydase

The upper gastrointestinal tract, including mouth, pharynx, and esophagus, is covered by a stratified epithelium, which is not keratinized but otherwise resembling that of epidermis. Hyaluronan fills the interstitium of the lower cell layers of these epithelia and gradually disappears when cells differentiate towards the surface Fig. 3a and b 28,29 . The decline of hyaluronan associated with the differentiation in the superficial esophageal epithelium is reversed in carcinoma in situ lesions,...

B CD44 Mediates the Internalization of Hyaluronan

The turnover of hyaluronan from the extracellular matrix occurs by essentially two mechanisms, local cell-mediated catabolism and or drainage into the lymphatic system for catabolism in regional lymph nodes, the liver and spleen 129,130 . Although the amount of hyaluronan turnover in some tissues such as the epidermis is high, there is little evidence to support the concept that hyaluronan is extensively degraded within the extracellular matrix. While there may be fragmentation of extracellular...

Elastic Offline Light Scattering Batch Mode

Zimm Plot For Molecular Weight

Average values of the molecular weight and of the size could be obtained by elastic offline LS, that is in batch mode. In batch LS mode a number of concentrations, usually from 3 to 5, is prepared and the intensity of the scattering is measured. Obviously in a MALS instrument the intensity of the scattering at different angles is also simultaneously measured by an array of photodiodes in each single scan. The concentration of the sample solutions has to be chosen on the basis of the...

Adipic Acid Dihy Drazide Ha

Figure 2 Chemical modifications of carboxylic acid groups of hyaluronan A esterification B carbodiimide modification C EDCI sulfo- NHS modification D EDCI hydrazide modification E thiol modification. drug-polymer conjugates, and crosslinked hydrogels. Hyaluronan-N-hydroxysuccinimide HA-NHS was synthesized by the reaction of N-hydroxysuccinimido diphenyl phosphate with the tetrabutylammonium salt of hyaluronan in DMSO. A hydrazide-containing fluorescent probe was condensed with HA-NHS to make a...

Animal Studies

Histochemical studies show that HA is a normal constituent of middle ear tissues although the functional significance of the occurrence of HA in the middle ear is still a matter of debate. Most probably it is the physico-chemical property of the molecule acting as a stress-absorber that results in its presence in the normal ear. The application in the abnormal ear has been proposed and experimentally evaluated in chronic tympanic membrane perforations. Topically applied HA applied to...

B Rhamm as a TACC

Rhamm Structure

The TACC family of proteins include human TACC3, murine TACC3, human TACC2 AZU-1 ECTACC, human TACC1, D-TACC and murine AINT 102 . Members of this family of proteins are defined by the presence of the so-called TACC domain, a predicted coiled-coil region in their carboxyl terminus 102 . In fact, the TACC proteins show the most similarity in this region as they share very little sequence identity throughout the rest of their protein sequence Fig. 3A 102 . In addition to the TACC domain, all...

Hyaluronan Based Biomaterials

Hylan Crosslink

To obtain materials that are mechanically and chemically robust, a variety of crosslinking strategies based on the chemistry described above have been explored to produce insoluble or gel-like hyaluronan materials. We separate hyaluronan-based biomaterials into two categories based on the crosslinking mechanism physical and chemical. In physical crosslinking, hydrophobic and ionic interactions convert hyaluronan or its derivatives into hydrogels. Chemically crosslinked materials have new...

Interaction of Hyaluronan with Phospholipids

Hyaluronan and phospholipids interact in an energetically favorable interaction and the type of lipid structures formed is influenced by the molecular weight of HA 5 . Even HA of 170 kDa, closer to the molecular weight of lung HA 220 kDa , organized 15-30 nm wide unilamellar vesicles into large aggregates. The aggregates were never observed in the absence of HA. In Fig. 2 is shown a model of how the water molecules bound to HA could interact directly with surfactant phospholipids in the lining...

Expression of Hyaluronan and Hyaluronidase in Cancer Cells of Epithelial Origin

The cancer cells are not always dependent on hyaluronan produced by adjacent stromal cells, but may have transformed into active hyaluronan synthesizers themselves. This is especially obvious in those cancers derived from epithelia normally negative for hyaluronan. Pronounced hyaluronan staining within malignant cells in human breast 27 , gastric Fig. 3e 37 , and colon Fig. 3h 36 cancers occurs frequently in vivo and makes the prognosis of these patients unfavorable. Recent experimental...

Future Directions

One major drawback in using HA as a lamina propria bioimplant for the treatment of vocal fold disorders is that its residence time within vocal folds is short, its half-life in rabbit vocal folds is only 3-5 days 7 . The half-life is most likely shorter in human vocal folds because of the effects of vibration and mechanical forces causing the glycoaminoglycan to breakdown faster. To overcome this obstacle, the HA molecular structure must be modified in order to have any meaningful residence...

D CD44Hyaluronan Interactions in Tumor Invasion and Metastasis

There is long standing evidence that many solid tumors are enriched in hyaluronan 163 . As far back as the beginning of the 20th century there was the description of a 'mucinous substance' associated with malignant breast carcinoma, analogous in nature to that found in umbilical cord 164 . Higher levels of hyaluronan are associated with poor prognoses in many cancers including human ovarian, breast and prostate carcinomas 165-168 . Coincident with this is the finding that CD44 is often...

Viscoaugmentation to Fill Facial Wrinkles and Depressed Scars

The first clinical trials using hylan B gel began in the late 1980s in Sweden and continued later in the USA 38,41,62 . These trials clearly showed that hylan B gel is a safe and effective material for facial tissue augmentation depending on the location used and, most importantly, on the precision of the application. When the gel is placed too deeply under the dermal fold into the loose connective tissue, the movements of the skin caused by massage and muscle movements for facial expressions...

Viscoaugmentation A Hyaluronan Gels

The first hyaluronan gel was prepared by Pharmacia AB Uppsala, Sweden in the early 1960s 36 by using 1,2,3,4-diepoxybutane as a cross-linking agent. This chemical has been widely used for cross-linking of polysaccharides such as cellulose and dextran. The epoxy cross-linked hyaluronan was prepared to be used for column chromatography and not for therapeutic use because of its poor biocompatibility. Water-insoluble hyaluronan gels for various therapeutic uses were first synthesized in the 1980s...

A CD44 Mediates the Retention of Hyaluronan Enriched Pericellular Matrices

Hyaluronic Acid Proteoglycan Cd44

In the presence of low concentrations of hyaluronan, cells that express hyalu-ronan receptors such as CD44 undergo cell-cell aggregation 4,108-110 . However, when the hyaluronan levels reach the point of saturation of available CD44 receptor sites, the cells disaggregate. The now independent cells remain autonomous within their own cell-associated or 'pericellular' matrix. These cell-associated pericellular matrices, often extending to a distance equal to the cell diameter, can be visualized...

Other Viscosurgical Uses

It was suggested in the early 1980s that elastoviscous hyaluronan solutions should be used as viscosurgical agents in transplantation surgery to protect surfaces of implants and transplants from mechanical damage and loss of water drying out 31 . It was also proposed that hyaluronan solutions with very high elastic and viscous properties should be used to protect tissues from mechanical damage by surgical tools or to create space for surgical manipulation during arthroscopic surgery 32 . The...

Conclusion

Hyaluronan has both structural and inflammatory properties in the lung. LMW HA may have an important role in inflammation as found in forms of ALI, including ARDS and VILI. Further study of LMW HA in forms of ALI may lead to new treatment options. 1. Meyer K, Palmer J. The polysaccharide of the vitreous humor. J Biol Chem 1934 107 629-634. 2. Laurent T. The biology of hyaluronan introduction. Ciba Found Symp 1989 143 1-5. 3. Weissman B, Meyer K. The structure of hyalobiuronic acid and of...

Elastoviscosity of Hyaluronan Solutions

Hyaluronan is an ubiquitous polysaccharide component of the intercellular matrix of all vertebrate tissues. It is not present in plants and insects, but the capsules of some bacteria contain it. In fluid tissue spaces like the synovial fluid of the joints and the liquid vitreus of the eye hyaluronan is present at a concentration and with an average molecular weight that provides these fluids with elastoviscous properties. This means that the tissue compartments containing such fluids can absorb...

Both Collagen and Elastin are Affected in Pulmonary Emphysema

In emphysema, major disruptions of the extracellular matrix occurs with a resulting enlargement of the air spaces. For many years, the focus has been on elastin since the most prominent histological change is a loss of elastin fibers particularly at junction points in the alveolar walls 98 . Chemically, there are changes in all components of the connective tissue including elastin 99 and the total elastin content of emphysematous lungs is less than for normal lungs 100 . It has been assumed...

Hyaluronan Size and Airway Pathophysiology

From the above given data, it is clear that hyaluronan plays an important role in the airway lumen it immobilizes certain molecules at the apical border of airway epithelial cells, thereby protecting them from mucociliary clearance. It also inhibits the activity of certain enzymes, e.g., TK. While being present there, it also does not seem to influence ciliary beating, a fact supported by a previous study showing that large molecular weight hyaluronan gt 1000 kDa , the size likely secreted into...

Protective Coating of Elastin Fibers

Heparan Sulfate Elastin

Recent data make it possible to picture HA and proteoglycans as part of the covering of elastic fibers. It has been known for a long time that amorphous elastin is covered with microfibrils. In early embryonic development, which can be as early as 23 h in the chick, elastin colocalized with fibrillin-1 and with fibulin-1 122 . Fibrillin-2 was also expressed at that stage and all three are known to be associated with cross-linked elastin. The elastic fiber assembly process involves association...

Light Scattering and Size Exclusion Chromatography

Stains All Hyaluronic Acid

Fundamental properties of hyaluronan, such as viscoelasticity and flow behavior primarily depend on the MWD, size, and conformation of the macromolecules. A primary method in estimating the molecular weight and the size of macromolecules is LS. LS and a few other methods such as osmometry, sedimentation, and mass spectrometry are absolute techniques. However, only the LS technique can be used online to a SEC system in obtaining the whole Figure 7 Agarose gel electrophoresis of nearly...

Historical Perspective

Hyaluronic Acid Random Coil

HA was initially discovered and named hyaluronic acid in a paper published in 1934 by Karl Meyer 6 . It was isolated from vitreous of the eye as a polysaccharide containing D-glucuronic acid and D-N-acetylglucosamine, but it was not until 20 years later that he completed the determination of its structure and showed that it contained a repeating b 1-3, 31-4 linked disaccharide. In the meantime, HA was isolated from many tissue sources, including synovial fluid, cock's comb and umbilical cord....

Conclusions

Hyaluronan is a critical ECM component in atherosclerosis and restenosis. Not only does it contribute to blood vessel wall thickening but also effects the biology of the vascular cells involved in vascular lesion progression. Attention needs to be given to understand the mechanism s responsible for hyaluronan accumulation in blood vessel disease as well as the molecular and signaling events that regulate the impact of hyaluronan on vascular cell phenotype. Targeting hyaluronan and or associated...

Contributors

Assistant Professor of Ophthalmology, Head of Ocular Surface Unit, Department of Surgical Sciences, Section of Ophthalmology, University of Messina, Italy Akira Asari, Ph.D. Manager, Glyco-Research Project, Central Research Laboratories, Seikagaku Corporation, Tokyo, Japan Luis Z. Avila, Ph.D. Principal Research Scientist, Genzyme Corporation, Cambridge, Massachusetts, U.S.A. Endre A. Balazs, M.D. Chairman, Matrix Biology Institute, Edgewater, New Jersey, and...

Brhamm Signaling in Cellular Motility

Rhamm Pathway

RHAMM is expressed on most cell types and has been shown to be involved in HA-mediated motility of lymphocytes 140 , hematopoietic cells 141,142 , sperm 143 , glial cells 129 , fibroblasts 130 and human umbilical vein endothelial cells 126,144 , as well as in tumor progression and metastasis 128, 145-149 . In some cell types, RHAMM is required for motility even though CD44 is also expressed 126,144,150 . Peptides corresponding to the HA-binding domains of RHAMM, or antibodies directed against...

Wound Healing

Following injury, the skin has a tremendous capacity to heal. When the injury involves disruption of the dermis, post-natal wounds heal with a macrophage-effected 8,9 fibro-proliferative repair process which results in the laying down of a new collagen-rich dermal matrix over which epidermal continuity can be reestablished. This process of repair and the subsequent reorganization of the dermal matrix results in scar formation. A scar is produced as the result of a reorganization of mesenchymal...

The LYVE1 and HARE Receptors for HA Endocytosis and Degradation

Throughout the body, HA is continuously synthesized and degraded, and the turnover of HA in mammalian tissues has been extensively studied 5,196-198 . HA levels in the extracellular milieu are carefully modulated, as the level of free HA influences a number of hydrodynamic systems in the organism, such as lung fluid balance 199 . High molecular mass HA is synthesized in the plasma membrane of fibroblasts and other cells by the addition of sugars to the reducing end of the growing polymer chain,...

Concluding Remarks and Outlook

The commonly held notion that enzymes secreted onto epithelial surfaces are rapidly cleared by mechanical action has been challenged by the results summarized in this chapter some luminal hyaluronan is immobilized at the apex of the airway epithelium where it can bind and retain secreted proteins. Since other mucosal secretions contain hyaluronan and possibly other glycosaminoglycans, these observations in the airway may also be relevant to other epithelia bathed in secretions and cleared by...

Structure of CD44 Primary Transcripts

Alternative Splicing Cd44

The CD44 gene is typically thought of as consisting of 20 exons Fig. 2 . Although a single gene is located on the short arm of human chromosome 11, multiple mRNA transcripts arise from the alternative splicing of 12 of the 20 Figure 2 The intron exon structure of the CD44 gene and pre-mRNA. Depicted are the 20 exons horizontal tube sections and introns intervening lines of the CD44 gene that give rise to a CD44 pre-mRNA and alternatively spliced CD44 mRNA. Depicted is the exon numbering of the...

Tissue Kallikrein and Hyaluronan Interaction and Enzyme Inhibition

Tissue kallikrein TK is a serine protease that generates lysyl-bradykinin in the airways by cleaving kininogens. Bradykinin is an important mediator of airway inflammation and has been implicated in the pathophysiology of asthma 29,30 . Tissue kallikrein is made in submucosal gland cells and secreted into the airway, albeit with inhibited enzymatic activity. The inhibition of TK activity in the airway was a puzzle as it is relatively insensitive, at least in vitro, to known serine protease...

Production by Lung Hyaluronidases

Hyaluronan is the natural substrate of hyaluronidases, a family of enzymes 54,55 which are discussed in a separate chapter of this book. At least two hyaluronidases are expressed in the lung. They are HYAL1 56 and HYAL2 57 , which was first described as a product of lung fibroblasts 58 and is expressed in many tissues. Both these enzymes are lysosomal enzymes and they degrade HA differently than testicular hyaluronidase and provide a large piece of approximately 20 kDa. The genes HYAL1, -2 and...

CD44 Receptor

Cd44 Receptor

CD44 proteins are class I transmembrane glycoproteins that bind HA and GAGs. CD44 has been shown to be expressed in most tissues and play a role in inflammation and immune function, organogenesis and development, malignancy and tissue homeostasis 7 . At the cellular level, CD44 can induce growth and survival 20,43,44 , endocytosis 37,45 , differentiation and maturation 46,47 , anchoring 48 , and motility 49,50 . CD44 is also important for resolution of inflammation in the lung following...

Agarose Gel Electrophoresis of High Molecular Weight Hyaluronan

Hyaluronic Acid Electrophoresis

Lee and Cowman 61 adapted methods used in the electrophoretic separation of high molecular weight nucleic acids for the separation of high molecular weight hyaluronan. They proposed the use of agarose gel at 0.5 in a continuous Tris-acetate-EDTA buffer for the separation of hyaluronan Fig. 6 . Sample loads of approximately 4-7 mg were required for polydisperse samples and the separated pattern was visualized by staining with the dye Stains-All For hyaluronan standards of known average molecular...

Viscometry A Theory

Plexus Nerves Hyaluronic Acid

Measurement of the viscosity of a solution containing hyaluronan allows the determination of the polymer viscosity-average close to the weight-average molecular weight. The theoretical basis for this effect is conceptually simple 1 . The Stokes-Einstein relation for the specific viscosity, -sp, of a dilute suspension of n spherical particles per unit volume of suspension, each with volume V, is where - and -0 are the respective viscosities of the suspension and pure fluid. The product, nV, is...

C CD44 Signaling for Cellular Motility and Adhesion

CD44 activation is associated with cell motility, especially in metastasizing cancer cells 50,83 . In some cancer cells, CD44 activity is specifically associated with cell motility, but not with growth 84,85 . The cytoplasmic domain of CD44 contains binding sites for several cytoskeleton-associated proteins including ezrin 86 and ankyrin 87,88 Fig. 1B . Ezrin is a member of the ERM family of structural proteins, which functions in both the organization of the actin cytoskeleton and the...

Analysis and Characterization of Hyaluronan Oligomers A Capillary Electrophoresis

Hyaluronic Acid Mass Spectrometry

The application of capillary electrophoresis CE for the analysis of acidic oligosaccharides has been an important development in the GAG field 60 . Its high-resolution separation, rapid analysis, quantitation of analytes, and low amount of sample usage makes it a very valuable analytical technique 61 . Procedures for the separation and identification of hyaluronan and its fragments by CE are well established 62,63 . In normal polarity mode sample application at anode and detection at cathode...

The Link Module Superfamily

The human Link module superfamily currently has 14 members and the majority of these contain a variety of other domain types Fig. 2 . Previously we have suggested 8 that this superfamily can be divided into three subgroups according to the known or expected size of their HA-binding domains HABDs see Fig. 3 . Type A domains are comprised of a single, independently folding Link module, as found in TSG-6 13,14 . The proteins KIA0527, Stabilin-1 and Stabilin-2, which all contain a single Link...

RHAMM is an Atypical Hyaladherin

HABPs or hyaladherins are conveniently divided into extracellular and cellular proteins Fig. 1 . Although with increasing characterization, this distinction is often blurred. For example, the cellular HABPs, CD44 and RHAMM can both be shed and occur as ECM proteins 69,70 . Cellular hyaladherins have been further classified according to their sequence homology e.g., CD44 and LYVE-1 CSRSBP-1 , the mechanism for their association with the cell surface and the mechanism by which they bind to HA 71...