Talin-dependent integrin activation is required for fibrin clot retraction by platelets
Talin-dependent integrin activation is required for fibrin clot retraction by platelets
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DOI：
10.1182/blood-2010-09-305433
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发表时间：
2011-02-03
期刊：
影响因子：
20.3
通讯作者：
Petrich, Brian G.
中科院分区：
文献类型：
--
作者：
Haling, Jacob R.;Monkley, Susan J.;Petrich, Brian G.
Talin作为整合素亲和力的调节剂和整合素与细胞骨架之间的重要机械连接发挥作用。使用基因缺失的塔林，我们首次表明，塔林激活整合素的能力所需的纤维蛋白凝块收缩血小板。为了进一步剖析这一过程所需的talin功能，我们测试了血小板中的凝块收缩表达talin 1（L325 R）突变体，结合整合素，但表现出受损的整合素激活归因于破坏之间的相互作用talin和膜近端区域（MPR）的β-整合素胞质结构域。Talin缺陷和Talin 1（L325 R）血小板在收缩纤维蛋白凝块方面存在缺陷。然而，talin 1（L325 R）血小板中的凝块收缩缺陷，而不是talin缺乏的血小板，通过用锰体外激活整合素来挽救，从而证明整合素激活是必需的，并表明talin 1（L325 R）可以与肌动蛋白细胞骨架形成功能性连接。（血。2011; 117（5）：1719-1722）
Talin functions both as a regulator of integrin affinity and as an important mechanical link between integrins and the cytoskeleton. Using genetic deletion of talin, we show for the first time that the capacity of talin to activate integrins is required for fibrin clot retraction by platelets. To further dissect which talin functions are required for this process, we tested clot retraction in platelets expressing a talin1(L325R) mutant that binds to integrins, but exhibits impaired integrin activation ascribable to disruption of the interaction between talin and the membrane-proximal region (MPR) in the beta-integrin cytoplasmic domain. Talin-deficient and talin1(L325R) platelets were defective in retracting fibrin clots. However, the defect in clot retraction in talin1(L325R) platelets, but not talin-deficient platelets, was rescued by extrinsically activating integrins with manganese, thereby proving that integrin activation is required and showing that talin1(L325R) can form functional links to the actin cytoskeleton. (Blood. 2011; 117(5): 1719-1722)