Hodivala-Dilke K M, DiPersio C M, Kreidberg J A, Hynes R O
Howard Hughes Medical Institute, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
J Cell Biol. 1998 Sep 7;142(5):1357-69. doi: 10.1083/jcb.142.5.1357.
Previously we found that alpha3beta1 integrin-deficient neonatal mice develop micro-blisters at the epidermal-dermal junction. These micro-blisters were associated with poor basement membrane organization. In the present study we have investigated the effect of alpha3beta1-deficiency on other keratinocyte integrins, actin-associated proteins and F-actin organization. We show that the absence of alpha3beta1 results in an increase in stress fiber formation in keratinocytes grown in culture and at the basal face of the basal keratinocytes of alpha3-null epidermis. Moreover, we see a higher concentration of actin-associated proteins such as vinculin, talin, and alpha-actinin at focal contact sites in the alpha3-deficient keratinocytes. These changes in focal contact composition were not due to a change in steady-state levels of these proteins, but rather to reorganization due to alpha3beta1 deficiency. Apart from the loss of alpha3beta1 there is no change in expression of the other integrins expressed by the alpha3-null keratinocytes. However, in functional assays, alpha3beta1 deficiency allows an increase in fibronectin and collagen type IV receptor activities. Thus, our findings provide evidence for a role of alpha3beta1 in regulating stress fiber formation and as a trans-dominant inhibitor of the functions of the other integrins in mouse keratinocytes. These results have potential implications for the regulation of keratinocyte adhesion and migration during wound healing.
此前我们发现，α3β1整合素缺陷的新生小鼠在表皮-真皮交界处会形成微水泡。这些微水泡与基底膜组织不良有关。在本研究中，我们调查了α3β1缺陷对其他角质形成细胞整合素、肌动蛋白相关蛋白和F-肌动蛋白组织的影响。我们发现，α3β1的缺失导致培养的角质形成细胞以及α3基因敲除表皮的基底角质形成细胞基底面的应力纤维形成增加。此外，我们在α3缺陷的角质形成细胞的粘着斑位点观察到肌动蛋白相关蛋白如纽蛋白、踝蛋白和α-辅肌动蛋白的浓度更高。粘着斑组成的这些变化并非由于这些蛋白质的稳态水平改变，而是由于α3β1缺陷导致的重组。除了α3β1缺失外，α3基因敲除的角质形成细胞表达的其他整合素的表达没有变化。然而，在功能试验中，α3β1缺陷会使纤连蛋白和IV型胶原受体活性增加。因此，我们的研究结果为α3β1在调节应力纤维形成中的作用以及作为小鼠角质形成细胞中其他整合素功能的反式显性抑制剂提供了证据。这些结果对伤口愈合过程中角质形成细胞粘附和迁移的调节具有潜在意义。
