ArticleThe Journal of biological chemistry2015
Fluorescence resonance energy transfer (FRET) and proximity ligation assays reveal functionally relevant homo- and heteromeric complexes among hyaluronan synthases HAS1, HAS2, and HAS3.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 37 citations in OpenAlex.
- Orcinol glucoside ameliorates pulmonary fibrosis by suppressing hyaluronic acid synthesis and macrophage M2 polarization via targeting hyaluronic acid synthase 2.International journal of molecular medicine · 2026Article
- Hyaluronan accumulation is associated with reduced hyaluronidase expression in renal cell carcinoma, with CD44, HAS1, and HYAL2 emerging as prognostic markers.The journal of pathology. Clinical research · 2025Article
- Hyaluronan: An Architect and Integrator for Cancer and Neural Diseases.International journal of molecular sciences · 2025Review
- The roles of hyaluronan in kidney development, physiology and disease.Nature reviews. Nephrology · 2024Review
- Golgi pH homeostasis stabilizes the lysosomal membrane throughLife science alliance · 2024Article
- Hyaluronan synthases; mechanisms, myths, & mysteries of three types of unique bifunctional glycosyltransferases.Glycobiology · 2023Review
- Hyaluronan in the Cancer Cells Microenvironment.Cancers · 2023Review
- Hyaluronic Acid: Known for Almost a Century, but Still in Vogue.Pharmaceutics · 2022Review
- Analysis of Human Hyaluronan Synthase Gene Transcriptional Regulation and Downstream Hyaluronan Cell Surface Receptor Mobility in Myofibroblast Differentiation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Angiostatic cues from the matrix: Endothelial cell autophagy meets hyaluronan biology.The Journal of biological chemistry · 2020Review
- HAS3-induced extracellular vesicles from melanoma cells stimulate IHH mediated c-Myc upregulation via the hedgehog signaling pathway in target cells.Cellular and molecular life sciences : CMLS · 2020Article
- The growth of a xenograft breast cancer tumor model with engineered hyaluronan-accumulating stroma is dependent on hyaluronan and independent of CD44.Oncotarget · 2019Article
- Increased Hyaluronan and TSG-6 in Association with Neuropathologic Changes of Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2019Article
- Hyaluronan Regulates Eyelid and Meibomian Gland Morphogenesis.Investigative ophthalmology & visual science · 2018Article
- Distinct reaction mechanisms for hyaluronan biosynthesis in different kingdoms of life.Glycobiology · 2018Article
- Extracellular matrix alterations in the Peyronie's disease.Journal of advanced research · 2017Article
- Article
- Hyaluronan-positive plasma membrane protrusions exist on mesothelial cells in vivo.Histochemistry and cell biology · 2016Article
- HYAL-2-WWOX-SMAD4 Signaling in Cell Death and Anticancer Response.Frontiers in cell and developmental biology · 2016Review
- Glycosyltransferase complexes in eukaryotes: long-known, prevalent but still unrecognized.Cellular and molecular life sciences : CMLS · 2016Review
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In vertebrates, hyaluronan is produced in the plasma membrane from cytosolic UDP-sugar substrates by hyaluronan synthase 1-3 (HAS1-3) isoenzymes that transfer N-acetylglucosamine (GlcNAc) and glucuronic acid (GlcUA) in alternative positions in the growing polysaccharide chain during its simultaneous extrusion into the extracellular space. It has been shown that HAS2 immunoprecipitates contain functional HAS2 homomers and also heteromers with HAS3 (Karousou, E., Kamiryo, M., Skandalis, S. S., Ruusala, A., Asteriou, T., Passi, A., Yamashita, H., Hellman, U., Heldin, C. H., and Heldin, P. (2010) The activity of hyaluronan synthase 2 is regulated by dimerization and ubiquitination. J. Biol. Chem. 285, 23647-23654). Here we have systematically screened in live cells, potential interactions among the HAS isoenzymes using fluorescence resonance energy transfer (FRET) and flow cytometric quantification. We show that all HAS isoenzymes form homomeric and also heteromeric complexes with each other. The same complexes were detected both in Golgi apparatus and plasma membrane by using FRET microscopy and the acceptor photobleaching method. Proximity ligation assays with HAS antibodies confirmed the presence of HAS1-HAS2, HAS2-HAS2, and HAS2-HAS3 complexes between endogenously expressed HASs. C-terminal deletions revealed that the enzymes interact mainly via uncharacterized N-terminal 86-amino acid domain(s), but additional binding site(s) probably exist in their C-terminal parts. Of all the homomeric complexes HAS1 had the lowest and HAS3 the highest synthetic activity. Interestingly, HAS1 transfection reduced the synthesis of hyaluronan obtained by HAS2 and HAS3, suggesting functional cooperation between the isoenzymes. These data indicate a general tendency of HAS isoenzymes to form both homomeric and heteromeric complexes with potentially important functional consequences on hyaluronan synthesis.
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