Dynamic catch of a Thy-1-α5β1+syndecan-4 trimolecular complex
Dynamic catch of a Thy-1-α5β1+syndecan-4 trimolecular complex
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DOI：
10.1038/ncomms5886
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发表时间：
2014-09-01
影响因子：
16.6
通讯作者：
Barker, Thomas H.
中科院分区：
文献类型：
--
作者：
Fiore, Vincent F.;Ju, Lining;Barker, Thomas H.
癌细胞与血管内皮细胞的黏附是肿瘤转移的关键步骤。内皮细胞表面分子Thy-1(CD90)通过与整合素和Syndecans的相互作用参与肿瘤的转移过程。然而，Thy-1如何在动态机械环境中支持细胞间的黏附尚不清楚。在这里，我们显示Thy-1支持β(1)整合素和Syndecan-4(Syn4)介导的黑色素瘤细胞收缩依赖的机械信号。在单分子水平上，Thy-1能够独立结合α(5)、β(1)整合素和Syndecan-4(Syndecan-4)受体。然而，在α(5)、β(1)和Syn4的存在下，这两个受体与Thy-1协同结合，形成三分子复合体。这种三分子络合物显示了一种独特的现象，我们称之为“动态捕捉”，其特征是键突然僵硬，随后形成捕捉键，其中力延长了键的寿命。因此，我们揭示了一类新的三分子相互作用，其中力加强了两个辅助受体的协同结合，并调节了下游的机械信号转导。
Cancer cell adhesion to the vascular endothelium is a critical step of tumour metastasis. Endothelial surface molecule Thy-1 (CD90) is implicated in the metastatic process through its interactions with integrins and syndecans. However, how Thy-1 supports cell-cell adhesion in a dynamic mechanical environment is not known. Here we show that Thy-1 supports beta(1) integrin- and syndecan-4 (Syn4)-mediated contractility-dependent mechanosignalling of melanoma cells. At the single-molecule level, Thy-1 is capable of independently binding alpha(5)beta(1) integrin and syndecan-4 (Syn4) receptors. However, in the presence of both alpha(5)beta(1) and Syn4, the two receptors bind cooperatively to Thy-1, to form a trimolecular complex. This trimolecular complex displays a unique phenomenon we coin 'dynamic catch', characterized by abrupt bond stiffening followed by the formation of catch bonds, where force prolongs the bond lifetime. Thus, we reveal a new class of trimolecular interactions where force strengthens the synergistic binding of two co-receptors and modulates downstream mechanosignalling.