FIBRONECTINS ROLE IN PERICELLULAR MATRIX ORGANIZATION

细胞粘附糖蛋白纤维连接蛋白（FN）在细胞内特异性沉积， 在胚胎发生过程中，迁移细胞遵循的途径，以及 作为大多数器官的细胞外基质的一部分。阻断 胚胎细胞与FN的相互作用引起了严重的干扰， 发展在成人中，循环血浆FN是由 肝脏，但似乎很少在其他组织中合成。然而，在这方面， 在创伤修复过程中，FN表达沿着 其他结缔组织成分，可能是多肽的结果 刺激FN的转化生长因子β等生长因子 和FN受体的表达，并且在胚胎发生过程中也起作用。细胞 用致癌病毒转化通常会失去它们的FN基质， 细胞-基质相互作用中的这种干扰可能是导致一些 转化表型的异常，甚至包括转移。 细胞通过特异性跨膜与含FN的基质相互作用 整合素的VLA亚家族中的受体。然而，我们已经证明， FN基质的沉积需要细胞的特异性结合， FN中与粘合剂相互作用的氨基末端位点 细胞受体因此，两个独立的细胞相互作用系统 有FN存在，一个用于沉积，另一个用于承认。因为 含FN的基质似乎在生长中起着至关重要的作用， 发展，伤口愈合和可能的肿瘤转移，这是重要的 了解它们是如何沉积的。为此，我们计划：1）隔离 并描述与FN相互作用的细胞表面分子 氨基末端29 kDa基质组装结构域。 2)研究结构-功能 氨基末端基质组装结构域中的关系， 重组DNA 3)阐明FN的基质组装体和细胞在细胞凋亡中的作用 粘附结构域结合细胞，并确定是否缺乏结合 FN的氨基末端基质组装结构域伴随致癌性 转型

The cell adhesive glycoprotein fibronectin (FN) is deposited in specific pathways during embryogenesis that are followed by migrating cells, and as part of the extracellular matrix in most organs. Blocking the interaction of embryonic cells with FN causes profound disturbances in development. In adults, circulating plasma FN is synthesized by the liver, but little appears to be synthesized in other tissues. However, during wound repair FN expression is coordinately increased along with other connective tissue components, possibly as a result of polypeptide growth factors such as transforming growth factor beta that stimulate FN and FN receptor expression and that also act during embryogenesis. Cells transformed with oncogenic viruses typically lose their FN matrices, and this disturbance in cell-matrix interaction may be responsible for some abnormalities of the transformed phenotype, including even metastasis. Cells interact with FN-containing matrices via specific transmembrane receptors in the VLA subfamily of integrins. However, we have shown that the deposition of FN matrices requires the specific binding of cells to an aminoterminal site in FN distinct that interacting with adhesive cellular receptors. Thus, two separate systems of cellular interactions with FN exist, one for deposition and the other for recognition. Because FN-containing matrices appear to play such a vital role in growth, development, wound healing and possible tumor metastasis, it is important to understand how they are deposited. To do this, we plan to: 1) Isolate and characterize the cell surface molecules interacting with FN's aminoterminal 29 kDa matrix assembly domain. 2) Study structure-function relationships in the aminoterminal matrix assembly domain using recombinant DNA. 3) Elucidate the role of FN's matrix assembly and cell adhesive domains in binding to cells, and determine if deficient binding of FN's aminoterminal matrix assembly domain accompanies oncogenic transformation.