KIAA1199, a deafness gene of unknown function, is a new hyaluronan binding protein involved in hyaluronan depolymerization

Hiroyuki Yoshida, Aya Nagaoka, Ayumi Kusaka-Kikushima, Megumi Tobiishi, Keigo Kawabata, Tetsuya Sayo, Shingo Sakai, Yoshinori Sugiyama, Hiroyuki Enomoto, Yasunori Okada, Shintaro Inoue

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5612-5617
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number14
DOIs
Publication statusPublished - 2013 Apr 2

Keywords

  • Extracellular matrix
  • Hearing loss
  • Hyaluronate
  • Hyaluronic acid

ASJC Scopus subject areas

  • General

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  • Cite this

    Yoshida, H., Nagaoka, A., Kusaka-Kikushima, A., Tobiishi, M., Kawabata, K., Sayo, T., Sakai, S., Sugiyama, Y., Enomoto, H., Okada, Y., & Inoue, S. (2013). KIAA1199, a deafness gene of unknown function, is a new hyaluronan binding protein involved in hyaluronan depolymerization. Proceedings of the National Academy of Sciences of the United States of America, 110(14), 5612-5617. https://doi.org/10.1073/pnas.1215432110