KIAA1199, a deafness gene of unknown function, is a new hyaluronan binding protein involved in hyaluronan depolymerization
| Autor: | Tetsuya Sayo, Aya Nagaoka, Yoshinori Sugiyama, Keigo Kawabata, Shingo Sakai, Hiroyuki Yoshida, Ayumi Kusaka-Kikushima, Hiroyuki Enomoto, Shintaro Inoue, Megumi Tobiishi, Yasunori Okada |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Immunoblotting Hyaluronoglucosaminidase Arthritis Biology GPI-Linked Proteins Real-Time Polymerase Chain Reaction Polymerization chemistry.chemical_compound Cell surface receptor Chlorocebus aethiops Hyaluronic acid medicine Animals Humans Immunoprecipitation Hyaluronic Acid Aged DNA Primers Glycosaminoglycans Gene knockdown Multidisciplinary Reverse Transcriptase Polymerase Chain Reaction Catabolism Cell adhesion molecule Synovial Membrane Proteins Transfection Fibroblasts Middle Aged Biological Sciences medicine.disease Molecular biology HEK293 Cells Hyaluronan Receptors medicine.anatomical_structure chemistry Gene Knockdown Techniques COS Cells Female RNA Interference Synovial membrane Cell Adhesion Molecules |
| Zdroj: | Proceedings of the National Academy of Sciences. 110:5612-5617 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1215432110 |
| Popis: | Hyaluronan (HA) has an extraordinarily high turnover in physiological tissues, and HA degradation is accelerated in inflammatory and neoplastic diseases. CD44 (a cell surface receptor) and two hyaluronidases (HYAL1 and HYAL2) are thought to be responsible for HA binding and degradation; however, the role of these molecules in HA catabolism remains controversial. Here we show that KIAA1199, a deafness gene of unknown function, plays a central role in HA binding and depolymerization that is independent of CD44 and HYAL enzymes. The specific binding of KIAA1199 to HA was demonstrated in glycosaminoglycan-binding assays. We found that knockdown of KIAA1199 abolished HA degradation by human skin fibroblasts and that transfection of KIAA1199 cDNA into cells conferred the ability to catabolize HA in an endo-β- N -acetylglucosaminidase–dependent manner via the clathrin-coated pit pathway. Enhanced degradation of HA in synovial fibroblasts from patients with osteoarthritis or rheumatoid arthritis was correlated with increased levels of KIAA1199 expression and was abrogated by knockdown of KIAA1199. The level of KIAA1199 expression in uninflamed synovium was less than in osteoarthritic or rheumatoid synovium. These data suggest that KIAA1199 is a unique hyaladherin with a key role in HA catabolism in the dermis of the skin and arthritic synovium. |
| Databáze: | OpenAIRE |
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