Thy-1-mediated cell-cell contact induces astrocyte migration through the engagement of αVβ3 integrin and syndecan-4.
Thy-1-mediated cell-cell contact induces astrocyte migration through the engagement of αVβ3 integrin and syndecan-4.
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DOI：
10.1016/j.bbamcr.2013.02.013
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发表时间：
2013-06
影响因子：
5.1
通讯作者：
Leyton, Lisette
中科院分区：
文献类型：
--
作者：
Kong, Milene;Munoz, Nicolas;Valdivia, Alejandra;Alvarez, Alvaro;Herrera-Molina, Rodrigo;Cardenas, Areli;Schneider, Pascal;Burridge, Keith;Quest, Andrew F. G.;Leyton, Lisette
细胞与细胞外基质（ECM）蛋白的粘附通过与结合Arg-Gly-Asp（RGD）三肽的整联蛋白和识别其他蛋白的肝素结合结构域（HBD）的多配体聚糖-4的相互作用而发生。这两种受体都能触发信号通路，包括那些激活RhoGTP酶如RhoA和Rac 1的通路。这一系列事件调节细胞与ECM的粘附和细胞迁移。使用神经元-星形胶质细胞模型，我们报道了神经元蛋白Thy-1与αVβ3整联蛋白和syndecan-4结合，诱导RhoA活化和星形胶质细胞与其底层基质的强粘附。因此，由于细胞间的相互作用和细胞对基质的牢固附着被认为是对细胞迁移的拮抗作用，我们假设Thy-1刺激星形胶质细胞应该阻止细胞迁移。在这里，我们研究了Thy-1表达神经元对星形胶质细胞极化和迁移的影响，使用伤口愈合试验和免疫荧光分析。通过亲和沉淀、蛋白质印迹和特异性抗体的使用来研究所涉及的信号分子。有趣的是，Thy-1与其两种受体的相互作用被发现增加星形胶质细胞的极化和迁移。后者的事件需要这些受体与RGD样序列和Thy-1的HBD的相互作用。此外，延长的Thy-1-受体相互作用抑制RhoA激活，同时激活FAK，PI 3 K和Rac 1。因此，整合素和syndecan-4与神经元表面蛋白Thy-1的持续参与诱导星形胶质细胞迁移。有趣的是，我们在这里确定，细胞-细胞相互作用，虽然最初诱导强烈的细胞附着，但在持续刺激下，通过与ECM蛋白刺激细胞运动所用的相同信号受体和分子接合，有利于细胞迁移。
Cell adhesion to the extracellular matrix (ECM) proteins occurs through interactions with integrins that bind to Arg-Gly-Asp (RGD) tripeptides, and syndecan-4, which recognizes the heparin-binding domain (HBD) of other proteins. Both receptors trigger signaling pathways, including those that activate RhoGTPases such as RhoA and Rac1. This sequence of events modulates cell adhesion to the ECM and cell migration. Using a neuron-astrocyte model, we have reported that the neuronal protein Thy-1 engages αVβ3 integrin and syndecan-4 to induce RhoA activation and strong astrocyte adhesion to their underlying substrate. Thus, because cell-cell interactions and strong cell attachment to the matrix are considered antagonistic to cell migration, we hypothesized that Thy-1 stimulation of astrocytes should preclude cell migration. Here, we studied the effect of Thy-1 expressing neurons on astrocyte polarization and migration using a wound-healing assay and immunofluorescence analysis. Signaling molecules involved were studied by affinity precipitations, western blots and the usage of specific antibodies. Intriguingly, Thy-1 interaction with its two receptors was found to increase astrocyte polarization and migration. The latter events required interactions of these receptors with both the RGD-like sequence and the HBD of Thy-1. Additionally, prolonged Thy-1-receptor interactions inhibited RhoA activation while activating FAK, PI3K and Rac1. Therefore, sustained engagement of integrin and syndecan-4 with the neuronal surface protein Thy-1 induces astrocyte migration. Interestingly we identify here, a cell-cell interaction that although initially induces strong cell attachment, upon persistant stimulation favors cell migration by engaging the same signaling receptors and molecules as those utilized by ECM proteins to stimulate cell movement.
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DOI：
10.1038/nrm2957
发表时间：
2010-09
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1016/j.bbamcr.2008.10.004
发表时间：
2009-05
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Barker TH;Hagood JS
通讯作者：
Hagood JS
影响因子：
3.7
作者：
Herrera-Molina R;Frischknecht R;Maldonado H;Seidenbecher CI;Gundelfinger ED;Hetz C;Aylwin Mde L;Schneider P;Quest AF;Leyton L
通讯作者：
Leyton L
影响因子：
4
作者：
Henriquez, Mauricio;Herrera-Molina, Rodrigo;Leyton, Lisette
通讯作者：
Leyton, Lisette
影响因子：
4
作者：
Pertz, Olivier
通讯作者：
Pertz, Olivier