ArticleCell research2012
A novel membrane-dependent on/off switch mechanism of talin FERM domain at sites of cell adhesion.
Article in Cell research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 116 citations in OpenAlex.
- Optimization of stapled peptide inhibitors reveals design principles for targeting talin-induced integrin activation.bioRxiv : the preprint server for biology · 2026Article
- FCHo2, not talin, enables inside-out activation of integrin ɑvβ5 in curved adhesions.Nature communications · 2026Article
- Skeletogenic Expression of Integrin Alpha, Talin and Npnt Genes and Npnt Role in Sea Urchin Skeletogenesis.Journal of experimental zoology. Part B, Molecular and developmental evolution · 2026Article
- Platelet Membrane Receptors and Signalling Pathways.Handbook of experimental pharmacology · 2026Review
- FCHo2, instead of talin, enables inside-out activation of integrin ɑvβ5 in curved adhesions.bioRxiv : the preprint server for biology · 2025Article
- Review
- Focal adhesion in the tumour metastasis: from molecular mechanisms to therapeutic targets.Biomarker research · 2025Review
- Biochemical and structural bases for talin ABSs-F-actin interactions.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- High-resolution snapshots of the talin auto-inhibitory states suggest roles in cell adhesion and signaling.Nature communications · 2024Article
- IL-13 and IL-17A activate β1 integrin through an NF-kB/Rho kinase/PIP5K1γ pathway to enhance force transmission in airway smooth muscle.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- IL-13 and IL-17A Activate β1 Integrin through an NF-kB/Rho kinase/PIP5K1γ pathway to Enhance Force Transmission in Airway Smooth Muscle.bioRxiv : the preprint server for biology · 2024Article
- Calpain Promotes LPS-induced Lung Endothelial Barrier Dysfunction via Cleavage of Talin.American journal of respiratory cell and molecular biology · 2023Article
- Article
- Inhibition of talin-induced integrin activation by a double-hit stapled peptide.Structure (London, England : 1993) · 2023Article
- Distinct bidirectional regulation of LFA1 and α4β7 by Rap1 and integrin adaptors in T cells under shear flow.Cell reports · 2023Article
- Article
- ConFERMing the role of talin in integrin activation and mechanosignaling.Journal of cell science · 2023Article
- Intrinsically disordered region of talin's FERM domain functions as an initial PIPBiophysical journal · 2023Article
- PI(4,5)P2: signaling the plasma membrane.The Biochemical journal · 2022Article
- Review
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
The activation of heterodimeric (α/β) integrin transmembrane receptors by cytosolic protein talin is crucial for regulating diverse cell-adhesion-dependent processes, including blood coagulation, tissue remodeling, and cancer metastasis. This process is triggered by the coincident binding of N-terminal FERM (four-point-one-protein/ezrin/radixin/moesin) domain of talin (talin-FERM) to the inner membrane surface and integrin β cytoplasmic tail, but how these binding events are spatiotemporally regulated remains obscure. Here we report the crystal structure of a dormant talin, revealing how a C-terminal talin rod segment (talin-RS) self-masks a key integrin-binding site on talin-FERM via a large interface. Unexpectedly, the structure also reveals a distinct negatively charged surface on talin-RS that electrostatically hinders the talin-FERM binding to the membrane. Such a dual inhibitory topology for talin is consistent with the biochemical and functional data, but differs significantly from a previous model. We show that upon enrichment with phosphotidylinositol-4,5-bisphosphate (PIP2) - a known talin activator, membrane strongly attracts a positively charged surface on talin-FERM and simultaneously repels the negatively charged surface on talin-RS. Such an electrostatic "pull-push" process promotes the relief of the dual inhibition of talin-FERM, which differs from the classic "steric clash" model for conventional PIP2-induced FERM domain activation. These data therefore unravel a new type of membrane-dependent FERM domain regulation and illustrate how it mediates the talin on/off switches to regulate integrin transmembrane signaling and cell adhesion.
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Registered trials
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.