Direct Thy-1/αVβ3 integrin interaction mediates neuron to astrocyte communication
Direct Thy-1/αVβ3 integrin interaction mediates neuron to astrocyte communication
复制标题
DOI：
10.1016/j.bbamcr.2008.01.034
复制
发表时间：
2008-06-01
影响因子：
5.1
通讯作者：
Leyton, Lisette
中科院分区：
文献类型：
--
作者：
Hermosilla, Tamara;Munoz, Daniel;Leyton, Lisette
THY-1是一种功能不明确的丰富的神经细胞糖蛋白。我们最近提供的证据表明，Thy-1聚集了星形胶质细胞中含有β(3)的整合素，以诱导酪氨酸磷酸化、RhoA激活以及局灶性粘连和应力纤维的形成。到目前为止，DI TNC1星形胶质细胞中β(3)整合素的阿尔法亚单位伙伴尚不清楚。类似地，神经元、膜结合的Thy-1通过整合素参与触发星形胶质细胞信号的能力仍在推测中。在此，获得了α(V)在DI TNC1星形胶质细胞中形成α(V)β(3)异二聚体的证据。在神经元-星形胶质细胞联合分析中，抗α(V)或抗β(3)整合素抗体的存在减少了细胞与细胞的相互作用，表明这两个整合素亚单位都是这种联系所必需的。此外，抗Thy-1抗体阻止了神经元对星形胶质细胞的刺激，但不能阻止这两种细胞的结合。因此，除了Thy-1整合素外，神经元-星形胶质细胞的结合还涉及分子之间的结合；然而，导致星形胶质细胞局灶性黏附形成的信号事件完全依赖于后者的相互作用。此外，表面等离子体共振分析表明，野生型(RLD)但未突变(RLE)的Thy-1与α(V)β(3)整合素直接相互作用。这种相互作用是由二价阳离子促进的，并且是物种无关的。综上所述，这些结果表明，α(V)、β(3)整合素异二聚体直接与神经细胞上存在的Thy-1相互作用，刺激星形胶质细胞。(C)2008爱思唯尔B.V.保留所有权利。
Thy-1 is an abundant neuronal glycoprotein of poorly defined function. We recently provided evidence indicating that Thy-1 clusters a beta(3)-containing integrin in astrocytes to induce tyrosine phosphorylation, RhoA activation and the formation of focal adhesions and stress fibers. To date, the alpha subunit partner of beta(3) integrin in DI TNC1 astrocytes is unknown. Similarly, the ability of neuronal, membrane-bound Thy-1 to trigger astrocyte signaling via integrin engagement remains speculation. Here, evidence that alpha(V) forms an alpha(V)beta(3) heterodimer in DI TNC1 astrocytes was obtained. In neuron-astrocyte association assays, the presence of either anti-alpha(V) or anti-beta(3) integrin antibodies reduced cell-cell interaction demonstrating the requirement of both integrin subunits for this association. Moreover, anti-Thy-1 antibodies blocked stimulation of astrocytes by neurons but not the binding of these two cell types. Thus, neuron-astrocyte association involved binding between molecular components in addition to the Thy-1-integrin; however, the signaling events leading to focal adhesion formation in astrocytes depended exclusively on the latter interaction. Additionally, wild-type (RLD) but not mutated (RLE) Thy-1 was shown to directly interact with alpha(V)beta(3) integrin by Surface Plasmon Resonance analysis. This interaction was promoted by divalent cations and was species-independent. Together, these results demonstrate that the alpha(V)beta(3) integrin heterodimer interacts directly with Thy-1 present on neuronal cells to stimulate astrocytes. (C) 2008 Elsevier B.V. All rights reserved.