EXTRACELLULAR MATRIX ASSEMBLY

细胞外基质组装

• 批准号: 2174512
• 负责人: ALBERT E CHUNG
• 金额: $ 25.01万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-01-01 至 1997-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2174512
• 关键词: Aves; PC12 cells; basement membrane; complementary DNA; entactin; exocytosis; extracellular matrix; gene expression; glycoprotein biosynthesis; glycoprotein structure; immunochemistry; laboratory mouse; laboratory rabbit; laminin; membrane biogenesis; membrane structure; messenger RNA; molecular cloning; monoclonal antibody; posttranslational modifications; protein sequence; protein structure function; tissue /cell culture; transfection /expression vector

The extracellular matrix plays a vital role in the normal function of complex organisms. It is implicated in organogenesis, cell differentiation, metastasis, neuronal guidance, wound healing and protective functions. A specialized sheet-like structure of the extracellular matrix, the basal lamina, underlies various tissues and is in intimate contact with the plasma membrane of the overlying cells. The major components of this structure are laminin, type IV collagen, heparan sulfate proteoglycan and entactin. The molecular structures of these molecules have been largely determined by recombinant DNA approaches and the biological activity of each molecule is being elucidated. The organization of the basement membrane varies with different tissues and undergoes dynamic changes during embryogenesis, wound healing, angiogenesis and in pathological states such as in infection, inflammation, and metastasis. Very little is known about how the basement membrane is synthesized and assembled in living organisms in the above situations. The purpose of this proposal is to examine the factors which regulate and otherwise influence the assembly of laminin and entactin into the extracellular matrix of cells and animals. The biosynthetic pathways for the extracellular matrix molecules will be manipulated with the aid of several cell lines that were selected for their distinctive characteristics. These lines will yield information on both the intracellular and extracellular fates of laminin and entactin as well as their interactions with other extracellular matrix components. As an animal model we propose to use the zebrafish, Brachydanio rerio . This small vertebrate organism has unique advantages over other vertebrates because of its size, ex corpora embryonic development, cost, and ease of genetic and biochemical manipulation. A combination of immunological, biochemical and genetic approaches will be used in these studies. It is hoped that the results obtained will contribute to our understanding of basal lamina function at the molecular level in normal development and in pathological conditions.

细胞外基质在正常功能中起着至关重要的作用 复杂的生物。它与器官发生有关 分化，转移，神经元引导，伤口愈合和 保护功能。专业的纸张结构 细胞外基质，基底层，是各种组织的基础 与上覆细胞的质膜紧密接触。这 该结构的主要组成部分是层粘连蛋白，IV型胶原蛋白，乙酰肝素 硫酸盐蛋白聚糖和肠蛋白。这些分子结构 分子已在很大程度上通过重组DNA方法确定，并且 每个分子的生物学活性正在阐明。这 地下室膜的组织随着不同的组织而变化 在胚胎发生，伤口愈合期间经历动态变化， 血管生成和病理状态（例如感染） 炎症和转移。 关于地下室的知识知之甚少 膜在上述生物中合成并组装 情况。该提案的目的是研究这些因素 调节并以其他方式影响层粘连蛋白和肠蛋白的组装 细胞和动物的细胞外基质。生物合成途径 对于细胞外基质分子，将借助 为其独特的几个细胞系 特征。 这些线将产生有关这两个方面的信息 层粘连蛋白和肠子蛋白的细胞内和细胞外命运以及 它们与其他细胞外基质组件的相互作用。作为 我们建议使用斑马鱼Brachydanio rerio。这 小脊椎动物比其他脊椎动物具有独特的优势 由于它的尺寸，ex Corpora胚胎开发，成本和便利性 遗传和生化操纵。 免疫学的结合， 这些研究将使用生化和遗传方法。 这是 希望获得的结果将有助于我们对 基底层层在分子水平的正常发育和 病理状况。