ADHESION MOLECULES AND LENS DEVELOPMENT

粘附分子和镜片开发

• 批准号: 2876139
• 负责人: A. Sue Menko
• 金额: $ 1.62万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2876139
• 关键词: Rous sarcoma virus; biological signal transduction; cell adhesion molecules; cell cell interaction; cell differentiation; chick embryo; cytoskeletal proteins; embryo /fetus tissue /cell culture; extracellular matrix; fluorescent dye /probe; gene expression; integrins; lens; microinjections; monoclonal antibody; phosphorylation; protein tyrosine kinase; temperature sensitive mutant; western blottings

Integrins are heterodimeric receptors which link the extracellular matrix to the cytoskeleton. They function beyond their role in adhesion, transmitting signals between the extracellular matrix (ECM) and the cell. Integrin mediated signalling has been shown to play a regulatory role in cellular differentiation. This grant focuses on the role of the integrin receptors, as both cell-substrate and cell-cell adhesion molecules, in lens development. Changes in integrin expression as a function of lens cell differentiation will be characterized in vivo. A chick embryo lens culture system will be used to characterize the mechanisms whereby i) integrins signal the initiation of lens differentiation and ii) changes in integrin interaction with the ECM regulates terminal lens differentiation. These lens cultures begin as an epithelial monolayer and differentiate to form multilayered lentoid structures. In the cultures the adhesion processes involved in lens differentiation can be manipulated both with antibodies to beta1 integrin and transformation with the src oncogene, both which result in a block of lens differentiation. I will examine the effects of antibodies to beta1 integrin and src on the organization of integrins in adhesion structures, on the association of cytoskeletal proteins with integrins in the adhesion structures and on the tyrosine phosphorylation of adhesion associated proteins. These studies will use immunocytochemical and biochemical techniques. Lens cultures transformed with the temperature sensitive src virus, tsLA24A, are a powerful tool for these studies in that they provide for the synchronous initiation of lens differentiation in culture. With the transformed lens cells it should be possible to describe the role of integrins in initiating and establishing the differentiation of lens cells in culture.

整合素是连接细胞外基质的异二聚体受体 到细胞骨架。它们在粘附中的作用超出了其作用， 在细胞外基质（ECM）和细胞之间传输信号。 整合素介导的信号传导已显示在 细胞分化。这项赠款专注于整合素的作用 受体，作为细胞基板和细胞 - 细胞粘附分子，在中 镜头发展。整联蛋白表达随镜头的函数的变化 细胞分化将在体内表征。小鸡胚胎镜头 培养系统将用于表征我的机制 整联蛋白信号镜头分化的启动和ii）变化 整联蛋白与ECM的相互作用调节末端晶状体分化。 这些晶状体培养是从上皮单层开始的，与 形成多层透镜结构。在文化中粘附 可以通过 beta1整联蛋白的抗体和使用SRC癌基因转化的抗体， 两者都导致一系列镜头分化。我将检查 抗体对Beta1整合素和SRC的抗体对组织的影响 粘附结构中的整合素，在细胞骨架的关联上 蛋白质在粘附结构和酪氨酸中的蛋白质 粘附相关蛋白的磷酸化。 这些研究将使用 免疫细胞化学和生化技术。镜头文化改变了 使用温度敏感的SRC病毒TSLA24A，是一个强大的工具 这些研究规定了镜头的同步启动 文化的分化。 使用转化后的透镜细胞应该是 可以描述整合素在启动和建立中的作用 培养基中晶状体细胞的分化。