Molecular mechanism for structure-dependent ligand recognition of the hyaluronan receptor

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17570098
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Structural biochemistry
• Research Institution: Shinshu University
• Principal Investigator: ITANO Naoki Shinshu University, Graduate School of Medicine, Associate professor (40257712)
• Project Period (FY): 2005 – 2006
• Keywords: Polysaccharide / Hyaluronan / Extracellular matrix / Structure / Interaction

Research Abstract

Hyaluronan (HA) is an extremely simple polysaccharide composed of repeating disaccharide units in which N-acetylglucosamine and glucuronic acid are linked together by alternating β-1,3 and β-1,4 linkages. The simple repeating structure of HA is involved in both a number of important cell behaviors and maintenance of tissue architecture. The multiple properties of HA depend largely on its molecular size, tissue concentration and the interaction with binding molecules. In this study, I examined the structural features of HA by scanning probe microscope. The three dimensional structure of HA changed dependently on its chain length and concentration. To examine the importance of HA structure in the ligand recognition of HA receptor CD44, I analyzed both affinity and kinetics of HA-CD44 interactions by surface plasmon resonance (SPR), and found that HA-binding molecule versican increased the affinity of CD44 to HA, suggesting that versican enhances the HA-CD44 interaction by altering HA structure. I then examined the effect of HA-binding molecule SHAP on the CD44-HA interaction-mediated cell adhesion. Under both static and flowing conditions, CD44-expressing cells adhered preferentially to the immobilized SHAP-HA complex than to HA alone, suggesting that SHAP enhances the interaction by increasing the avidity of HA to CD44.

Research Products

• [Journal Article] Hyperproduction of Hyaluronan in Neu-Induced Mammary Tumor Accelerates Angiogenesis through Stromal Cell Recruitment: Possible Involvement of Versican/PG-M. (2007)
  • Author(s): Koyama, H., Hibi, T., Isogai, Z., Yoneda, M., Fujimori, M., Amano, J., Kawakubo, M., Kannagi, R., Kimata, K., Taniguchi, S., and Itano, N.
  • Journal Title: American Journal of Pathology 170(3) Pages: 1086-1099
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Hyperproduction of Hyaluronan in Neu-Induced Mammary Thmor Accelerates Angiogenesis through Stromal Cell Recruitment : Possible Involvement of Versican /PG-M. (2007)
  • Author(s): Koyama, H., Hibi, T., Isogai, Z., Yoneda, M. Fujimori, M., Amano, J., Kawakubo, M. Kannagi, R., Kimata, K., Taniguchi, S., Itano, N.
  • Journal Title: American Journal of Pathology 170(3) Pages: 1086-1099
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] SHAP potentiates the CD44-mediated leukocyte adhesionto the hyaluronan substratum (2006)
  • Author(s): Zhuo, L., Kanamori, A., Kannagi, R., Itano, N., Wu, J., Hamaguchi, N., Kimata, K.
  • Journal Title: Journal of Biologicla Chemistry 281(29) Pages: 20303-20314
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] SHAP Potentiates the CD44-mediated Leukocyte Adhesion to the Hyaluronan Substratum (2006)
  • Author(s): Zhuo, L., Kanamori, A. Kannagi, R., Itano. N. Wu, J., Hamaguchi, M., Ishiguro, N., Kimata, K.
  • Journal Title: Journal of Biological Chemistry 281(29) Pages: 20303-20314
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] ヒアルロン酸合成酵素未来を拓く糖鎖科学(永井克孝監修) (2005)
  • Author(s): 板野 直樹, 木全 弘治
  • Total Pages: 2
  • Publisher: 金芳堂
  • Description: 「研究成果報告書概要(和文)」より
• [Book] プロテオグリカン分子群の合成と構造異常がもたらす細胞機能の変化-癌浸潤・転移の理解と克服に向けた解析-未来を拓く糖鎖科学(永井克孝監修) (2005)
  • Author(s): 板野 直樹
  • Total Pages: 6
  • Publisher: 金芳堂
  • Description: 「研究成果報告書概要(和文)」より