正常止血需要Talin自身抑制。

IF 2.6 3区 医学 Q3 CELL BIOLOGY
Platelets Pub Date : 2025-12-01 Epub Date: 2025-09-08 DOI:10.1080/09537104.2025.2555197
Bhavya Venkatesh, Kalyan Golla, Felix Hong, Amanda Haage, Hugh Kim, Guy Tanentzapf
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引用次数: 0

摘要

细胞外基质(ECM)粘附受体整合素家族在血小板功能中起核心作用,包括粘附和聚集。在静止的血小板中,整合素以低亲和力状态存在于它们的配体中,并在配体结合到细胞外结构域或细胞质蛋白(如talin)结合到细胞内β-尾时被激活。Talin的功能是通过自抑制调节的,这降低了其整合素激活功能。因此,阻断talin自抑制的点突变Tln1E1770A会增加整合素的激活并破坏成纤维细胞的细胞迁移。在这里,我们发现talin自身抑制在止血过程中也起着重要作用。Tln1E1770A突变小鼠在尾出血试验中表现出出血缺陷。此外,从Tln1E1770A小鼠中分离的血小板表现出聚集破坏和凝块收缩延迟,表明整合素信号传导存在缺陷。然而,在talin自身抑制缺陷的血小板中,整合素的激活并没有增加,这表明talin在血小板中的作用不同于内向外的整合素信号传导。综上所述,我们的数据表明talin自身抑制是止血过程中血小板的重要调节机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Talin autoinhibition is required for normal hemostasis.

The integrin family of extracellular matrix (ECM) adhesion receptors plays a central role in platelet function, including adhesion and aggregation. In resting platelets, integrins exist in a low-affinity state for their ligands, and are activated upon ligand binding to the extracellular domain or binding of cytoplasmic proteins such as talin to the intracellular β-tail. Talin function is regulated through autoinhibition, which reduces its integrin-activating function. A point mutation that blocks talin autoinhibition, Tln1E1770A, therefore increases integrin activation and disrupts cell migration in fibroblasts. Here, we show that talin autoinhibition also plays an important role during hemostasis. Tln1E1770A mutant mice display defective hemostasis when examined using a tail bleeding assay. Furthermore, platelets isolated from Tln1E1770A mice exhibit disrupted aggregation and delayed clot retraction, indicating a defect in integrin signaling. However, integrin activation was not increased in platelets with defective talin autoinhibition, suggesting a different role for talin in platelets, distinct from inside-out integrin signaling. Taken together, our data shows that talin autoinhibition is an important regulatory mechanism in platelets during hemostasis.

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来源期刊
Platelets
Platelets 医学-细胞生物学
CiteScore
6.70
自引率
3.00%
发文量
79
审稿时长
1 months
期刊介绍: Platelets is an international, peer-reviewed journal covering all aspects of platelet- and megakaryocyte-related research. Platelets provides the opportunity for contributors and readers across scientific disciplines to engage with new information about blood platelets. The journal’s Methods section aims to improve standardization between laboratories and to help researchers replicate difficult methods. Research areas include: Platelet function Biochemistry Signal transduction Pharmacology and therapeutics Interaction with other cells in the blood vessel wall The contribution of platelets and platelet-derived products to health and disease The journal publishes original articles, fast-track articles, review articles, systematic reviews, methods papers, short communications, case reports, opinion articles, commentaries, gene of the issue, and letters to the editor. Platelets operates a single-blind peer review policy. Authors can choose to publish gold open access in this journal.
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