Association of β1 integrin with focal adhesion kinase and paxillin in differentiating Schwann cells
Association of β1 integrin with focal adhesion kinase and paxillin in differentiating Schwann cells
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DOI：
10.1523/jneurosci.20-10-03776.2000
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发表时间：
2000-05-15
影响因子：
5.3
通讯作者：
Fernandez-Valle, C
中科院分区：
文献类型：
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作者：
Chen, LM;Bailey, D;Fernandez-Valle, C
当雪旺细胞（SCs）同时附着在轴突和基板上时，可分化为成髓鞘细胞。我们感兴趣的是定义由基底膜激活的信号通路。通过SC/感觉神经元(N)共培养，我们发现β 1整合素和f -肌动蛋白是导致髓磷脂基因表达和髓鞘形成的途径的组成部分（Fernandez-Valle等人，1994,1997）。本研究表明，在没有基底层的情况下，局部粘附激酶（FAK）和paxillin在sc接触轴突时组成性地表达。FAK和paxillin的酪氨酸磷酸化随着sc形成基底层和分化而增加。FAK和paxillin在SC/N共培养中特异性地与β 1整合素共免疫沉淀，而不是SC单独培养。Paxillin与FAK和fyn激酶在SC/N共培养中的共免疫沉淀。一部分酪氨酸磷酸化的b1整合素、FAK和paxillin分子存在于分化共培养物的不溶性、富含f -肌动蛋白的部分中。细胞松弛素D是一种肌动蛋白解聚剂，可降低FAK和paxillin的酪氨酸磷酸化及其与b1整合素的关联，并导致不溶性FAK和paxillin复合物丰度的剂量依赖性增加。总的来说，我们的工作表明，b1整合素、FAK、paxillin和fyn激酶在轴突存在的情况下，在SCs中形成一个肌动蛋白相关复合物，粘附在基底层。这种复合物可能对SC向髓鞘细胞分化的过程起重要作用。
Schwann cells (SCs) differentiate into a myelinating cell when simultaneously adhering to an axon destined for myelination and basal lamina. We are interested in defining the signaling pathway activated by basal lamina. Using SC/sensory neuron (N) cocultures, we identified beta 1 integrin and F-actin as components of a pathway leading to myelin gene expression and myelination (Fernandez-Valle et al., 1994, 1997). Here, we show that focal adhesion kinase (FAK) and paxillin are constitutively expressed by SCs contacting axons in the absence of basal lamina. Tyrosine phosphorylation of FAK and paxillin increases as SCs form basal lamina and differentiate. FAK and paxillin specifically coimmunoprecipitate with beta 1 integrin in differentiating SC/N cocultures but not SC-only cultures. Paxillin coimmunoprecipitates with FAK and fyn kinase in differentiating SC/N cocultures. A subset of tyrosine-phosphorylated b1 integrin, FAK, and paxillin molecules reside in the insoluble, F-actin-rich fraction of differentiating cocultures. Cytochalasin D, an actin depolymerizing agent, decreases tyrosine phosphorylation of FAK and paxillin and their association with b1 integrin and causes a dose-dependent increase in the abundance of insoluble FAK and paxillin complexes. Collectively, our work indicates that b1 integrin, FAK, paxillin, and fyn kinase form an actin-associated complex in SCs adhering to basal lamina in the presence of axons. This complex may be important for initiating the process of SC differentiation into a myelinating cell.