The assembly of integrin adhesion complexes requires both extracellular matrix and intracellular rho/rac GTPases.
The assembly of integrin adhesion complexes requires both extracellular matrix and intracellular rho/rac GTPases.
复制标题
DOI：
10.1083/jcb.131.6.1857
复制
发表时间：
1995-12
期刊：
影响因子：
--
通讯作者：
Hall A
中科院分区：
文献类型：
--
作者：
Hotchin NA;Hall A
细胞与细胞外基质通过整联蛋白粘附受体的相互作用在广泛的细胞功能中发挥着重要作用，例如细胞生长、运动和分化。与底物相互作用后，整联蛋白聚集并与多种细胞质蛋白结合，形成焦点复合物并与肌动蛋白细胞骨架结合。尽管整合素诱导的细胞内信号目前尚不清楚，但人们认为它们是由聚集到焦点复合物的蛋白质介导的。例如，有人提出，在招募到粘着斑后，p125FAK 可以激活 ERK1/2 MAP 激酶级联。我们之前曾报道过，小 GTP 酶 rho 家族的成员在细胞中激活时可以触发焦点复合物的组装。利用显微注射技术，我们现在已经研究了细胞外基质和两种 GTP 结合蛋白 rac 和 rho 在小鼠和人类成纤维细胞整合素复合物组装中的作用。我们发现整合素与细胞外基质的相互作用不足以诱导整合素聚集和局灶复合物形成。类似地，在缺乏基质的情况下，细胞外生长因子激活 rho 或 rac 不会导致局灶复合物形成。焦点复合物仅在基质和 rho 家族功能活性成员同时存在的情况下才能组装。与此一致的是，在没有 rho/rac 活性的情况下，整合素与基质的相互作用无法激活 Swiss 3T3 细胞中的 ERK1/2 激酶。事实上，ERK1/2 在没有基质的情况下可以被生长因子完全激活，因此，成纤维细胞生长的粘附依赖性似乎不太可能是通过 ras/MAP 激酶途径介导的。我们得出的结论是，在缺乏功能活跃的 rho GTP 家族成员的情况下，细胞外基质不足以触发焦点复合物组装和随后的整合素依赖性信号转导。
Interaction of cells with extracellular matrix via integrin adhesion receptors plays an important role in a wide range of cellular: functions, for example cell growth, movement, and differentiation. Upon interaction with substrate, integrins cluster and associate with a variety of cytoplasmic proteins to form focal complexes and with the actin cytoskeleton. Although the intracellular signals induced by integrins are at present undefined, it is thought that they are mediated by proteins recruited to the focal complexes. It has been suggested, for example, that after recruitment to focal adhesions p125FAK can activate the ERK1/2 MAP kinase cascade. We have previously reported that members of the rho family of small GTPases can trigger the assembly of focal complexes when activated in cells. Using microinjection techniques, we have now examined the role of the extracellular matrix and of the two GTP-binding proteins, rac and rho, in the assembly of integrin complexes in both mouse and human fibroblasts. We find that the interaction of integrins with extracellular matrix alone is not sufficient to induce integrin clustering and focal complex formation. Similarly, activation of rho or rac by extracellular growth factors does not lead to focal complex formation in the absence of matrix. Focal complexes are only assembled in the presence of both matrix and functionally active members of the rho family. In agreement with this, the interaction of integrins with matrix in the absence of rho/rac activity is unable to activate the ERK1/2 kinases in Swiss 3T3 cells. In fact, ERK1/2 can be activated fully by growth factors in the absence of matrix and it seems unlikely, therefore, that the adhesion dependence of fibroblast growth is mediated through the ras/MAP kinase pathway. We conclude that extracellular matrix is not sufficient to trigger focal complex assembly and subsequent integrin-dependent signal transduction in the absence of functionally active members of the rho family of GTPases.