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

透明质酸受体结构依赖性配体识别的分子机制

• 批准号: 17570098
• 负责人: ITANO Naoki
• 金额: $ 2.3万
• 依托单位: Shinshu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17570098/
• 关键词: Polysaccharide; Hyaluronan; Extracellular matrix; Structure; Interaction; ヒアルロン酸; 糖鎖; 受容体; 細胞外マトリックス

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.

透明质酸（HA）是一种极其简单的多糖，由重复的双糖单元组成，其中n -乙酰氨基葡萄糖和葡萄糖醛酸通过交替的β-1,3和β-1,4键连接在一起。透明质酸的简单重复结构参与了许多重要的细胞行为和组织结构的维持。透明质酸的多种特性在很大程度上取决于其分子大小、组织浓度以及与结合分子的相互作用。在本研究中，我通过扫描探针显微镜检查了HA的结构特征。透明质酸的三维结构随其链长和浓度的变化而变化。为了研究HA结构在HA受体CD44配体识别中的重要性，我通过表面等离子体共振（SPR）分析了HA-CD44相互作用的亲和力和动力学，发现HA结合分子versican增加了CD44对HA的亲和力，这表明versican通过改变HA结构来增强HA-CD44相互作用。然后，我检查了ha结合分子SHAP对CD44-HA相互作用介导的细胞粘附的影响。在静态和流动条件下，表达CD44的细胞都优先粘附于固定的SHAP-HA复合物，而不是单独粘附于HA，这表明SHAP通过增加HA对CD44的亲和力来增强相互作用。

项目成果

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)

蛋白多糖分子的合成和结构异常引起的细胞功能变化 - 理解和克服癌症侵袭和转移的分析 - 开辟未来的糖科学（永井胜隆监修）

• 发表时间: 2005
• 作者: 板野 直樹;木全 弘治;板野 直樹
• 通讯作者: 板野 直樹

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)

开辟未来的透明质酸合成酶糖科学（永井胜隆监修）

• 发表时间: 2005
• 作者: 板野 直樹;木全 弘治
• 通讯作者: 木全 弘治

Hyperproduction of hyaluronan in Neu-induced mammary tumor accelerates angiogenesis through stromal cell recruitment - Possible involvement of versican/PG-M

• DOI: 10.2353/ajpath.2007.060793
• 发表时间: 2007-03-01
• 期刊: AMERICAN JOURNAL OF PATHOLOGY
• 影响因子: 6
• 作者: Koyama, Hiroshi;Hibi, Terumasa;Itano, Naoki
• 通讯作者: Itano, Naoki

Hyperproduction of Hyaluronan in Neu-Induced Mammary Thmor Accelerates Angiogenesis through Stromal Cell Recruitment : Possible Involvement of Versican /PG-M.

Neu 诱导的乳腺癌中透明质酸的过度生成通过基质细胞募集加速血管生成：Versacan /PG-M 可能参与其中。

• 发表时间: 2007
• 期刊: American Journal of Pathology 170(3)
• 作者: Koyama;H.;Hibi;T.;Isogai;Z.;Yoneda;M. Fujimori;M.;Amano;J.;Kawakubo;M. Kannagi;R.;Kimata;K.;Taniguchi;S.;Itano;N.
• 通讯作者: N.

SHAP potentiates the CD44-mediated leukocyte adhesion to the hyaluronan substratum

• DOI: 10.1074/jbc.m506703200
• 发表时间: 2006-07-21
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Zhuo, Lisheng;Kanamori, Akiko;Kimata, Koji
• 通讯作者: Kimata, Koji