The Talin Head Domain Binds to Integrin β Subunit Cytoplasmic Tails and Regulates Integrin Activation
Open accessAbstract
The beta subunit cytoplasmic domains of integrin adhesion receptors are necessary for the connection of these receptors to the actin cytoskeleton. The cytoplasmic protein, talin, binds to beta integrin cytoplasmic tails and actin filaments, hence forming an integrin-cytoskeletal linkage. We used recombinant structural mimics of beta(1)A, beta(1)D and beta(3) integrin cytoplasmic tails to characterize integrin-binding sites within talin. Here we report that an integrin-binding site is localized within the N-terminal talin head domain. The binding of the talin head domain to integrin beta tails is specific in that it is abrogated by a single point mutation that disrupts integrin localization to talin-rich focal adhesions. Integrin-cytoskeletal interactions regulate integrin affinity for ligands (activation). Overexpression of a fragment of talin containing the head domain led to activation of integrin alpha(IIb)beta(3); activation was dependent on the presence of both the talin head domain and the integrin beta(3) cytoplasmic tail. The head domain of talin thus binds to integrins to form a link to the actin cytoskeleton and can thus regulate integrin function.
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A 150 nM (10 μg ml−1) concentration of Ang2 stimulates FN7-10 binding to CHO cells equally well as ectopic expression of the talin head domain.
“Of note, a 150 nM (10 μg ml−1) concentration of Ang2 stimulated FN7–10 binding to CHO cells equally well as the ectopic expression of the talin head domain, a prominent inside-out activator of β1-integrin44.”
From Endothelial destabilization by angiopoietin-2 via integrin β1 activation (2015) · cites this paper as [44]
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- Authors
- Calderwood, D. A., Zent, R., Grant, R., Rees, D. J. G., Hynes, R. O., & Ginsberg, M. H.
- Affiliations
- Scripps Research Institute (US)
- University of the Western Cape (ZA)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Ginsberg, Mark H.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-10
- Volume
- 274
- Issue
- 40
- Pages
- 28071-28074
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2088544660
- Cited by
- 720
- References
- 0
- Citations by year
- 2026: 9 · 2025: 19 · 2024: 10 · 2023: 22 · 2022: 15 · 2021: 18 · 2020: 24 · 2019: 22 · 2018: 15 · 2017: 34 · 2016: 32 · 2015: 24 · 2014: 27 · 2013: 23 · 2012: 41
- FWCI
- 10.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- National Institutes of Health (5p01hl048728-10, AR27214, CA17007)
- National Heart, Lung, and Blood Institute (HL 59007, HL-48728)
- National Cancer Institute (CA 17007, R01CA017007)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Keywords
- talin, integrin activation, focal adhesions, integrin αIIbβ3, CD61, actin cytoskeleton, integrin binding site
- MeSH terms
- Amino Acid Sequence, Chromatography, Affinity, Cytoplasm, Humans, Molecular Sequence Data, Protein Binding, Protein Conformation, Recombinant Proteins, Talin, Integrin beta1
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