Evidence map›Paper›PMID 30988001›Full record

ArticleThe Journal of cell biology2019

Rap1 binding and a lipid-dependent helix in talin F1 domain promote integrin activation in tandem.

Alexandre R Gingras, Frederic Lagarrigue, Monica N Cuevas, Andrew J Valadez, Marcus Zorovich, Wilma McLaughlin, Miguel Alejandro Lopez-Ramirez, Nicolas Seban, Klaus Ley, William B Kiosses and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of cell biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
5.5field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 51 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Divergent Functions of Rap1A and Rap1B in Endothelial Biology and Disease.International journal of molecular sciences · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Spatial Mechano-Signaling Regulation of GTPases through Non-Degradative Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
  12. [Molecular dynamics simulation of force-regulated interaction between talin and Rap1b].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2023
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 2 institutions in 1 country.

Alexandre R Gingras *Department of Medicine, University of California, San Diego, La Jolla, CA agingras@ucsd.edu.ORCID 0000-0002-5373-0176
Frederic Lagarrigue *Department of Medicine, University of California, San Diego, La Jolla, CA.
Monica N CuevasDepartment of Medicine, University of California, San Diego, La Jolla, CA.
Andrew J ValadezDepartment of Medicine, University of California, San Diego, La Jolla, CA.
Marcus ZorovichDepartment of Medicine, University of California, San Diego, La Jolla, CA.
Wilma McLaughlinDepartment of Medicine, University of California, San Diego, La Jolla, CA.
Miguel Alejandro Lopez-RamirezDepartment of Medicine, University of California, San Diego, La Jolla, CA.ORCID 0000-0001-7089-4060
Nicolas SebanDepartment of Medicine, University of California, San Diego, La Jolla, CA.ORCID 0000-0002-6737-6681
Klaus LeyDivision of Inflammation Biology, La Jolla Institute for Immunology, La Jolla, CA.
William B KiossesMicroscopy Core Facility, La Jolla Institute for Immunology, La Jolla, CA.
Mark H GinsbergDepartment of Medicine, University of California, San Diego, La Jolla, CA mhginsberg@ucsd.edu.ORCID 0000-0002-5685-5417
University of California San Diego · USLa Jolla Institute for Immunology · US

Funding

The Interaction of TPO and Integrins in Hematopoiesis CellsP01HL078784 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GINSBERG, MARK HOWARD · 2005 to 2019
$28.3M
The Hemostasis, Thrombosis, and Inflammation Models CoreP01HL151433 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Mark HOWARD Ginsberg · 2020 to 2026
$16.4M
Deconvoluting the Vascular AdhesomeR35HL139947 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GINSBERG, MARK HOWARD · 2018 to 2024
$5.5M
Regulation of endothelial gene expression by cerebral cavernous malformation complexK01HL133530 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI LOPEZ-RAMIREZ, MIGUEL ALEJANDRO · 2018 to 2022
$903k
Super-resolution confocal microscopeS10OD021831 · OD · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI LEY, KLAUS F. · 2017 to 2017
$566k
NHLBI NIH HHS K01 HL133530NHLBI NIH HHS P01 HL078784NHLBI NIH HHS P01 HL151433NHLBI NIH HHS R35 HL139947NIH HHS S10 OD021831
6 · The paper itself

Abstract

Rap1 GTPases bind effectors, such as RIAM, to enable talin1 to induce integrin activation. In addition, Rap1 binds directly to the talin1 F0 domain (F0); however, this interaction makes a limited contribution to integrin activation in CHO cells or platelets. Here, we show that talin1 F1 domain (F1) contains a previously undetected Rap1-binding site of similar affinity to that in F0. A structure-guided point mutant (R118E) in F1, which blocks Rap1 binding, abolishes the capacity of Rap1 to potentiate talin1-induced integrin activation. The capacity of F1 to mediate Rap1-dependent integrin activation depends on a unique loop in F1 that has a propensity to form a helix upon binding to membrane lipids. Basic membrane-facing residues of this helix are critical, as charge-reversal mutations led to dramatic suppression of talin1-dependent activation. Thus, a novel Rap1-binding site and a transient lipid-dependent helix in F1 work in tandem to enable a direct Rap1-talin1 interaction to cause integrin activation.

Indexed as

AnimalsBinding SitesCHO CellsCricetinaeCricetulusHumansIntegrinsLipidsMutationProtein BindingProtein ConformationProtein DomainsShelterin ComplexTalinTelomere-Binding ProteinsIntegrinsLipidsShelterin ComplexTalinTelomere-Binding ProteinsTERF2IP protein, humanTLN1 protein, human

Identifiers

PMID30988001
PMCPMC6548133
OpenAlexW2939943074

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

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.