CYTOSKELETON-MEMBRANE INTERACTIONS--ANTISERUM INDUCED C

该项目的总体长期目标是获得更大的 了解细胞基质粘附的分子基础。 细胞与细胞外基质接触会影响细胞骨架 组织，细胞增殖和表达 分化的细胞产物。 细胞可以反过来修改基质 回应接触。 细胞对基质的这种重塑是一种新的生物学机制。 正常发展和维护的重要特征 正常的组织更新 改变了控制 正常的细胞-基质通讯会导致发育缺陷 或转移。 细胞对某些基质有不止一种受体 配体，如纤连蛋白和层粘连蛋白。 这些分子还 有不止一个细胞结合位点。 这就提出了一个 问题是什么样的信号正在传输到 由于特定类型的表面， 受体-细胞外基质接触。 的一个大科 结构相关的异源二聚体细胞表面粘附受体 复合物，称为整合素，能够与几个 细胞外基质配体。 以前的研究表明， 几个重要的迁移过程所需的受体 例如神经突生长、哺乳动物胚泡基质 肿瘤细胞的相互作用、神经嵴迁移和附着 到基底膜。 整合素传递信号的能力 将在一个系统中研究细胞表面的 通过针对整联蛋白纤连蛋白的特异性抗体结合 受体，引起细胞骨架重组，诱导 基质降解金属内蛋白酶的细胞表达。 如果贴壁细胞暴露于短时间内， 含有arg-gly-asp细胞识别序列的肽 存在于被整合素识别的基质配体中。 努力将集中在确定其他整合素的结合是否 特异性抗体可以诱导这些蛋白酶， 蛋白酶的诱导需要细胞骨架重组， 这种信号的传递是由G蛋白调节的， 蛋白酶的表达有协同变化 抑制剂、细胞外基质配体或整联蛋白受体 由于这种束缚。 C-DNA探针和特异性 抗体将用于检测细胞的这些方面， 反应 在另一项研究中，将使用粘附变体 其整联蛋白的表达可以在20倍范围内调节 5-溴脱氧尿苷 特异性抗体识别 受调节的整合素二聚体复合物的单个亚基 将用于脉冲追踪研究，以确定 蛋白质水平的缺陷。 针对个体的C-DNA探针 亚基将被用来比较mRNA表达水平， 遵守和不遵守的国家。 综上所述各项 研究应该加强我们对生物学作用的理解， 调节这类非常重要的细胞的表达 基质粘附受体

The overall, long term goal of this project is to gain a greater understanding of the molecular basis of cell matrix adhesion. Cell-extracellular matrix contact can effect cytoskeletal organization, cell proliferation and the expression of differentiated cell products. Cells can in turn modify the matrix in response to contact. Such remodelling of matrix by cells is an important feature of normal development and the maintenance of normal tissue renewal. Alterations in the mechanisms that control normal cell-matrix communication can lead to developmental defects or metastasis. Cells have more than one receptor for some matrix ligands, such as fibronectin and laminin. These molecules also have more than one binding site for cells. This raises the question as to what kinds of signals are being transmitted to the interior of the cell as a result of a particular type of surface receptor-extracellular matrix contact. A large family of structurally related heterodimeric cell surface adhesion receptor complexes, called integrins, are able to interact with several extracellular matrix ligands. Previous studies have shown these receptors to be required for several important migratory processes such as neurite outgrowth, mammalian blastocyst-matrix interactions, neural crest migration and attachment of tumor cells to basement membrane. The ability of integrin to transmit signals across the cell surface will be studied in a system in which the binding by a specific antibody against the integrin fibronectin receptor, which causes cytoskeletal reorganization, induces the expression by the cell of matrix degrading metalloendoproteinases. A similar effect is found if adherent cells are exposed to short peptides containing the arg-gly-asp cell recognition sequence present in matrix ligands that are recognized by integrins. Efforts will focus on determining if the binding of other integrins by specific antibodies can induce these proteases, whether induction of protease requires cytoskeletal reorganization, whether transmission of this signal is regulated by G proteins and whether there is coordinate alteration in the expression of protease inhibitors, extracellular matrix ligands or the integrin receptors themselves as a result of this binding. C-DNA probes and specific antibodies will be used to detect these aspects of the cellular response. In a separate study, adhesion variants will be used whose expression of integrins can be modulated over a 20 fold range by 5-bromodeoxyuridine. Specific antibodies that recognize individual subunits of the regulated integrin dimeric complexes will be used in pulse chase studies to determine the nature of the defect at the protein level. C-DNA probes against individual subunits will be used to compare the levels of mRNA expression in the adherent and non adherent states. Taken together, these studies should enhance our understanding of the biological role and regulation of expression of this very important class of cell matrix adhesion receptors.