ArticleThe Journal of biological chemistry2009
Two novel functions of hyaluronidase-2 (Hyal2) are formation of the glycocalyx and control of CD44-ERM interactions.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 74 citations in OpenAlex.
- Naive CD4iScience · 2026Article
- The association between blood-basedLung cancer management · 2025Article
- Hyaluronan: An Architect and Integrator for Cancer and Neural Diseases.International journal of molecular sciences · 2025Review
- Genetic Deficiencies of Hyaluronan Degradation.Cells · 2024Review
- Hyaluronan Receptors as Mediators and Modulators of the Tumor Microenvironment.Advanced healthcare materials · 2023Review
- Key Role of Hyaluronan Metabolism for the Development of Brain Metastases in Triple-Negative Breast Cancer.Cells · 2022Article
- Methods for isolating and analyzing physiological hyaluronan: a review.American journal of physiology. Cell physiology · 2022Review
- Matters of size: Roles of hyaluronan in CNS aging and disease.Ageing research reviews · 2021Review
- Myofibroblasts: Function, Formation, and Scope of Molecular Therapies for Skin Fibrosis.Biomolecules · 2021Review
- Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns (With video).Burns & trauma · 2021Article
- Hyaluronidase-2 Regulates RhoA Signaling, Myofibroblast Contractility, and Other Key Profibrotic Myofibroblast Functions.The American journal of pathology · 2020Article
- Role of Moesin Phosphorylation in Retinal Pericyte Migration and Detachment Induced by Advanced Glycation Endproducts.Frontiers in endocrinology · 2020Article
- The U3 and Env Proteins of Jaagsiekte Sheep Retrovirus and Enzootic Nasal Tumor Virus Both Contribute to Tissue Tropism.Viruses · 2019Article
- High levels of serum hyaluronan is an early predictor of dengue warning signs and perturbs vascular integrity.EBioMedicine · 2019Article
- Article
- Targeting Hyaluronan Interactions for Glioblastoma Stem Cell Therapy.Cancer microenvironment : official journal of the International Cancer Microenvironment Society · 2019Article
- Article
- A mammalian homolog of the zebrafish transmembrane protein 2 (TMEM2) is the long-sought-after cell-surface hyaluronidase.The Journal of biological chemistry · 2017Article
- Hyaluronan activates Hyal-2/WWOX/Smad4 signaling and causes bubbling cell death when the signaling complex is overexpressed.Oncotarget · 2017Article
- A Trickster in Disguise: Hyaluronan's Ambivalent Roles in the Matrix.Frontiers in oncology · 2017Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It has long been predicted that the members of the hyaluronidase enzyme family have important non-enzymatic functions. However, their nature remains a mystery. The metabolism of hyaluronan (HA), their major enzymatic substrate, is also enigmatic. To examine the function of Hyal2, a glycosylphosphatidylinositol-anchored hyaluronidase with intrinsically weak enzymatic activity, we have compared stably transfected rat fibroblastic BB16 cell lines with various levels of expression of Hyal2. These cell lines continue to express exclusively the standard form (CD44s) of the main HA receptor, CD44. Hyal2, CD44, and one of its main intracellular partners, ezrin-radixin-moesin (ERM), were found to co-immunoprecipitate. Functionally, Hyal2 overexpression was linked to loss of the glycocalyx, the HA-rich pericellular coat. This effect could be mimicked by exposure of BB16 cells either to Streptomyces hyaluronidase, to HA synthesis inhibitors, or to HA oligosaccharides. This led to shedding of CD44, separation of CD44 from ERM, reduction in baseline level of ERM activation, and markedly decreased cell motility (50% reduction in a wound healing assay). The effects of Hyal2 on the pericellular coat and on CD44-ERM interactions were inhibited by treatment with the Na(+)/H(+) exchanger-1 inhibitor ethyl-N-isopropylamiloride. We surmise that Hyal2, through direct interactions with CD44 and possibly some pericellular hyaluronidase activity requiring acidic foci, suppresses the formation or the stability of the glycocalyx, modulates ERM-related cytoskeletal interactions, and diminishes cell motility. These effects may be relevant to the purported in vivo tumor-suppressive activity of Hyal2.
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