BIOLOGICAL FUNCTIONS OF ENTACTIN

描述：细胞外基质在正常情况下起着至关重要的作用 复杂生物体的功能。它与器官发生、细胞 分化、转移、神经引导、伤口愈合和 具有保护功能。的专用片状结构。 细胞外基质是基底膜，位于各种组织和 与上面细胞的质膜密切接触。这个 这种结构的主要成分是层粘连蛋白、IV型胶原、Perlecan 和entactin/nidogen。这项提案涉及到的生物学功能 肌动蛋白作为基底膜的主要成分。Entactin是一种 由1217个氨基酸残基组成的硫酸化糖蛋白。分子 被组织成结构域和功能域，这些域涉及 与层粘连蛋白、IV型胶原、纤维连接蛋白、Perlecan、纤溶蛋白和 纤维蛋白原。据信，entactin的一个主要结合点是组织 和基底膜的稳定。此外，entactin和 牙本质蛋白衍生的多肽促进细胞的附着和铺展 几种类型的细胞，并促进趋化和吞噬功能 中性粒细胞。Entactin基因的失活会导致胚胎 小鼠的致死表型。这个项目的目的是扩大 Entactin在小鼠胚胎发育、器官发育中作用的研究 组织功能的发展和维持。在这些研究中 Entactin基因特定区域的突变将被引入到 小鼠通过改良的胚胎干细胞。这些努力将是 辅以灭活牙本质蛋白基因的实验 特异性组织通过cre重组酶/loxP系统。胚胎和 将对突变动物的组织进行分析，以将突变与 肌动蛋白与组织形态和功能。希望这一结果 这将有助于我们对基底膜功能的理解 正常发育和病理状态下的分子水平。

DESCRIPTION: 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 basement membrane, 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, perlecan and entactin/nidogen. This proposal addresses the biological functions of entactin as a major component of the basement membrane. Entactin is a sulfated glycoprotein consisting of 1217 amino acid residues. The molecule is organized into structural and functional domains that are engaged in interactions with laminin, collagen IV, fibronectin, perlecan, fibulin and fibrinogen. A major junction of entactin is believed to be the organization and stabilization of the basement membrane. In addition, entactin and peptides derived from entactin enhance the attachment and spreading of several types of cells and promote both chemotaxis and phagocytosis in neutrophils. The inactivation of the entactin gene results in an embryonic lethal phenotype in the mouse. It is the purpose of this project to extend the studies on the role that entactin plays in mouse embryogenesis, organ development, and maintenance of tissue functions. In these studies mutations in specific regions of the entactin gene will be introduced into mice by means of modified embryonic stem cells. These efforts will be complemented with experiments to inactivate the gene for entactin in specific tissues by the cre recombinase/loxP system. The embryos and tissues of the mutant animals will be analyzed to correlate the mutations in entactin with tissue morphology and function. 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.