ArticleBiophysical journal2020
Kindlin Assists Talin to Promote Integrin Activation.
Article in Biophysical journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 39 citations in OpenAlex.
- The interaction between inflammation and estrogen in adenomyosis : from molecular mechanisms to therapeutic strategies.Seminars in immunopathology · 2026Review
- Integrins in Cancer Drug Resistance: Molecular Mechanisms and Clinical Implications.International journal of molecular sciences · 2025Review
- The role and regulation of integrins in cell migration and invasion.Nature reviews. Molecular cell biology · 2025Review
- Paxillin and Kindlin: Research Progress and Biological Functions.Biomolecules · 2025Review
- Integrins as Key Mediators of Metastasis.International journal of molecular sciences · 2025Review
- Nanoscopy reveals integrin clustering reliant on kindlin-3 but not talin-1.Cell communication and signaling : CCS · 2025Article
- Integrin mechanosensing relies on a pivot-clip mechanism to reinforce cell adhesion.Biophysical journal · 2024Article
- Advances in modeling cellular mechanical perceptions and responses via the membrane-cytoskeleton-nucleus machinery.Mechanobiology in medicine · 2024Review
- Integrins in cancer stem cells.Frontiers in cell and developmental biology · 2024Review
- Talin and kindlin use integrin tail allostery and direct binding to activate integrins.Nature structural & molecular biology · 2023Article
- Kindlin stabilizes the talin·integrin bond under mechanical load by generating an ideal bond.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- The Multifunctional Protein Syntenin-1: Regulator of Exosome Biogenesis, Cellular Function, and Tumor Progression.International journal of molecular sciences · 2023Review
- The complex relationship between integrins and oncolytic herpes Simplex Virus 1 in high-grade glioma therapeutics.Molecular therapy oncolytics · 2022Review
- On modeling the multiscale mechanobiology of soft tissues: Challenges and progress.Biophysics reviews · 2022Review
- Molecular determinants of αVβ5 localization in flat clathrin lattices - role of αVβ5 in cell adhesion and proliferation.Journal of cell science · 2022Article
- New insights into regulation of αIIbβ3 integrin signaling by filamin A.Research and practice in thrombosis and haemostasis · 2022Article
- Solubilization and Purification of αMethods in molecular biology (Clifton, N.J.) · 2022Article
- Integrin-Mediated Tumorigenesis and Its Therapeutic Applications.Frontiers in oncology · 2022Review
- Upregulated Talin1 synergistically boosts β-estradiol-induced proliferation and pro-angiogenesis of eutopic and ectopic endometrial stromal cells in adenomyosis.Reproductive biology and endocrinology : RB&E · 2021Article
- Talin1 Induces Epithelial-Mesenchymal Transition to Facilitate Endometrial Cell Migration and Invasion in Adenomyosis Under the Regulation of microRNA-145-5p.Reproductive sciences (Thousand Oaks, Calif.) · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Integrin αIIbβ3 is a predominant type of integrin abundantly expressed on the surface of platelets and its activation regulates the process of thrombosis. Talin and kindlin are cytoplasmic proteins that bind to integrin and modulate its affinity for extracellular ligands. Although the molecular details of talin-mediated integrin activation are known, the mechanism of kindlin involvement in this process remains elusive. Here, we demonstrate that the interplay between talin and kindlin promotes integrin activation. Our all-atomic molecular dynamics simulations on complete transmembrane and cytoplasmic domains of integrin αIIbβ3, talin1 F2/F3 subdomains, and the kindlin2 FERM domain in an explicit lipid-water environment over a microsecond timescale unraveled the role of kindlin as an enhancer of the talin interaction with the membrane proximal region of β-integrin. The cooperation of kindlin with talin results in a complete disruption of salt bridges between R995 on αIIb and D723/E726 on β3. Furthermore, kindlin modifies the molecular mechanisms of inside-out activation by decreasing the crossing angle between transmembrane helices of integrin αIIbβ3, which eventually results in parallelization of integrin dimer. In addition, our control simulation featuring integrin in complex with kindlin reveals that kindlin binding is not sufficient for unclasping the inner-membrane and outer-membrane interactions of integrin dimer, thus ruling out the possibility of solitary action of kindlin in integrin activation.
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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.