Institute of Hospital Management, West China Hospital, Sichuan University, 37 Guoxue Rd., Chengdu, Sichuan Province, China.
Department of Vascular Surgery, West China Hospital, Sichuan University, 37 Guoxue Rd., Chengdu, Sichuan Province, China.
Protein J. 2018 Jun;37(3):280-289. doi: 10.1007/s10930-018-9776-8.
Bi-directional signaling of integrins plays an important role in platelet and leukocyte function. Talin plays a key role in integrin bi-directional signaling and its binding to integrin is highly regulated. The precise regulation of the recruitment and binding of talin to integrin is still being elucidated. In particular, the recruitment of talin to integrin is controlled by the RAP-1 and RIAM/lamellipodin signaling axis and the affinity between talin and integrin is regulated by the conformation or protease cleavage of talin. However, whether the binding between integrin and talin is also regulated by integrin conformation has not been thoroughly explored before. In this work, we used biochemical binding assays to study the potential role of integrin conformational changes in integrin-talin interactions. Constitutively active integrin αIIbb3 binds markedly stronger to talin than inactive αIIbb3. Inactive αIIbb3 markedly increases its binding to talin once activated, regardless of how αIIbb3 is activated. Further, the increased binding to talin is b3 tail dependent. Our results suggest that integrin conformation is another regulatory mechanism for integrin-talin interaction.
整合素的双向信号转导在血小板和白细胞功能中起着重要作用。塔林在整合素的双向信号转导中起着关键作用，其与整合素的结合受到高度调节。塔林与整合素的募集和结合的精确调节仍在阐明中。特别是，塔林向整合素的募集受 RAP-1 和 RIAM/片状蛋白信号轴的控制，而塔林与整合素之间的亲和力受塔林构象或蛋白酶切割的调节。然而，整合素构象是否也调节整合素与塔林之间的结合尚未得到深入研究。在这项工作中，我们使用生化结合测定来研究整合素构象变化在整合素-塔林相互作用中的潜在作用。组成性激活的整合素 αIIbb3 与塔林的结合明显强于非活性的 αIIbb3。一旦激活，非活性的 αIIbb3 会明显增加与塔林的结合，而无论 αIIbb3 如何被激活。此外，增加与塔林的结合依赖于 b3 尾部。我们的结果表明，整合素构象是整合素-塔林相互作用的另一种调节机制。
