ArticleBlood2014
A talin mutant that impairs talin-integrin binding in platelets decelerates αIIbβ3 activation without pathological bleeding.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 48 citations in OpenAlex.
- Optimization of stapled peptide inhibitors reveals design principles for targeting talin-induced integrin activation.bioRxiv : the preprint server for biology · 2026Article
- Inside-out integrin activation is essential for early mammalian development.Molecular biology of the cell · 2025Article
- How Protein Depletion Balances Thrombosis and Bleeding Risk in the Context of Platelet's Activatory and Negative Signaling.International journal of molecular sciences · 2024Review
- Mechanosensory entities and functionality of endothelial cells.Frontiers in cell and developmental biology · 2024Review
- IL-2 can signal via chemokine receptors to promote regulatory T cells' suppressive function.Cell reports · 2023Article
- Talin variant P229S compromises integrin activation and associates with multifaceted clinical symptoms.Human molecular genetics · 2022Article
- Reversible Platelet Integrin αIIbβ3 Activation and Thrombus Instability.International journal of molecular sciences · 2022Review
- Review
- Force-enhanced biophysical connectivity of platelet β3 integrin signaling through Talin is predicted by steered molecular dynamics simulations.Scientific reports · 2022Article
- Article
- The extracellular matrix of hematopoietic stem cell niches.Advanced drug delivery reviews · 2022Review
- Talin-dependent integrin activation is required for endothelial proliferation and postnatal angiogenesis.Angiogenesis · 2021Article
- Integrin affinity modulation critically regulates atherogenic endothelial activation in vitro and in vivo.Matrix biology : journal of the International Society for Matrix Biology · 2021Article
- Distinct integrin activation pathways for effector and regulatory T cell trafficking and function.The Journal of experimental medicine · 2021Article
- Manipulation of Focal Adhesion Signaling by Pathogenic Microbes.International journal of molecular sciences · 2021Review
- Comparison of the central human and mouse platelet signaling cascade by systems biological analysis.BMC genomics · 2020Article
- Loss ofBlood science (Baltimore, Md.) · 2020Article
- The New Weapon to Inhibit Proliferation and Migration of Smooth Muscle Cell in Neointimal Formation.Korean circulation journal · 2020Article
- Anti-D4GDI antibodies activate platelets in vitro: a possible link with thrombocytopenia in primary antiphospholipid syndrome.Arthritis research & therapy · 2019Article
- Talin-Dependent Integrin Activation Regulates VE-Cadherin Localization and Endothelial Cell Barrier Function.Circulation research · 2019Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Tight regulation of integrin affinity is critical for hemostasis. A final step of integrin activation is talin binding to 2 sites within the integrin β cytoplasmic domain. Binding of talin to a membrane-distal NPxY sequence facilitates a second, weaker interaction of talin with an integrin membrane-proximal region (MPR) that is critical for integrin activation. To test the functional significance of these distinct interactions on platelet function in vivo, we generated knock-in mice expressing talin1 mutants with impaired capacity to interact with the β3 integrin MPR (L325R) or NPLY sequence (W359A). Both talin1(L325R) and talin1(W359A) mice were protected from experimental thrombosis. Talin1(L325R) mice, but not talin(W359A) mice, exhibited a severe bleeding phenotype. Activation of αIIbβ3 was completely blocked in talin1(L325R) platelets, whereas activation was reduced by approximately 50% in talin1(W359A) platelets. Quantitative biochemical measurements detected talin1(W359A) binding to β3 integrin, albeit with a 2.9-fold lower affinity than wild-type talin1. The rate of αIIbβ3 activation was slower in talin1(W359A) platelets, which consequently delayed aggregation under static conditions and reduced thrombus formation under physiological flow conditions. Together our data indicate that reduction of talin-β3 integrin binding affinity results in decelerated αIIbβ3 integrin activation and protection from arterial thrombosis without pathological bleeding.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.