MOLECULAR MECHANISMS OF CELL SUBSTRATE INTERACTIONS

细胞基质相互作用的分子机制

• 批准号: 3839286
• 负责人: S K AKIYAMA
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3839286
• 关键词: biological signal transduction; cell adhesion; cell cell interaction; cell migration; cellular pathology; embryogenesis; fibronectins; integrins; molecular biology; molecular pathology; monoclonal antibody; protein structure function; receptor binding; receptor expression; wound healing

Interactions of fibronectin with its integrin receptors play important roles in embryonic development, wound healing and the progression of diseases such as cancer. Approaches involving monoclonal antibodies, molecular and cell biology, and physical chemistry are being employed to elucidate molecular mechanisms underlying the interactions of fibronectin with integrins with the goal of understanding the roles of these glycoproteins in complex biological processes in order to develop bioadhesive substrates and to provide the bases for rational medical intervention in diseases involving abnormal cellular adhesion and migration Besides the RGD and the synergistic regions on fibronectin, a third site to the amino-terminal side of the synergistic region has been identified that is required for assembly of fibronectin matrices in vivo, though not for binding of fibronectin to integrins. Fibronectin- integrin interactions are not required for fibroblast-mediated collagen gel contraction nor for odontoblast differentiation, although such interactions play a role in the adhesion of these cells. Up-regulation of keratinocyte migration during wound healing depends on the redistribution of integrins, expression of the alpha5beta1 fibronectin receptor integrin, and the acquisition of a migratory phenotype. Studies currently underway will examine the three-dimensional structure of the fibronectin cell-adhesive region in solution, and the role of integrins in transmembrane signal transduction.

纤维连接蛋白与其整合素受体的相互作用起重要作用 在胚胎发育、伤口愈合和 疾病，如癌症。 涉及单克隆抗体的方法， 分子和细胞生物学以及物理化学被用来 阐明相互作用的分子机制 纤连蛋白与整合素的目的是了解的作用， 这些糖蛋白在复杂的生物过程中， 生物粘附基质，并为合理的医疗保健提供基础。 干预涉及异常细胞粘附的疾病， 除了纤维连接蛋白上的RGD和协同区域外， 协同区域的氨基末端侧的第三位点已经被 确定了在细胞中组装纤连蛋白基质所需的 体内，但不用于纤连蛋白与整联蛋白的结合。 纤连蛋白- 成纤维细胞介导的胶原不需要整合素相互作用 凝胶收缩也不用于成牙本质细胞分化，尽管这样 相互作用在这些细胞的粘附中起作用。 上调 在伤口愈合过程中角质形成细胞迁移的影响取决于 整合素的再分布，α 5 β 1纤连蛋白的表达 受体整联蛋白和迁移表型的获得。 目前正在进行的研究将检查三维结构 的纤维连接蛋白细胞粘附区域在溶液中，和的作用， 整合素在跨膜信号转导中的作用。