Novel roles for alpha3beta1 integrin as a regulator of cytoskeletal assembly and as a trans-dominant inhibitor of integrin receptor function in mouse keratinocytes.
Novel roles for alpha3beta1 integrin as a regulator of cytoskeletal assembly and as a trans-dominant inhibitor of integrin receptor function in mouse keratinocytes.
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DOI：
10.1083/jcb.142.5.1357
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发表时间：
1998-09-07
期刊：
影响因子：
--
通讯作者：
Hynes RO
中科院分区：
文献类型：
--
作者：
Hodivala-Dilke KM;DiPersio CM;Kreidberg JA;Hynes RO
以前我们发现α3β1整合素缺陷的新生小鼠在表皮-真皮交界处产生微水泡。这些微水泡与基底膜组织不良有关。在本研究中，我们研究了α3β1缺乏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的缺乏导致在培养中生长的角质形成细胞和α3缺失表皮的基底角质形成细胞的基底面的应力纤维形成增加。此外，在α3缺陷的角质形成细胞中，我们在局部接触部位观察到更高浓度的肌动蛋白相关蛋白，如黏着斑蛋白、talin和α-actinin。局灶性接触成分的这些变化不是由于这些蛋白质的稳态水平变化，而是由于α3β1缺乏引起的重组。除了α3β1的丢失之外，由α3缺失的角质形成细胞表达的其他整联蛋白的表达没有变化。然而，在功能测定中，α3β1缺乏可增加纤连蛋白和IV型胶原蛋白受体活性。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的意义。
Previously we found that α3β1 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 α3β1-deficiency on other keratinocyte integrins, actin-associated proteins and F-actin organization. We show that the absence of α3β1 results in an increase in stress fiber formation in keratinocytes grown in culture and at the basal face of the basal keratinocytes of α3-null epidermis. Moreover, we see a higher concentration of actin-associated proteins such as vinculin, talin, and α-actinin at focal contact sites in the α3-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 α3β1 deficiency. Apart from the loss of α3β1 there is no change in expression of the other integrins expressed by the α3-null keratinocytes. However, in functional assays, α3β1 deficiency allows an increase in fibronectin and collagen type IV receptor activities. Thus, our findings provide evidence for a role of α3β1 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.
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影响因子：
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