Evidence map›Paper›PMID 32989126›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Evolutionarily diverse LIM domain-containing proteins bind stressed actin filaments through a conserved mechanism.

Jonathan D Winkelman, Caitlin A Anderson, Cristian Suarez, David R Kovar, Margaret L Gardel

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.

0numbers the graph read from it
0cells of the map it votes in
78citing papers in PubMed
7.7field-weighted citation impact, top 2% 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

78 citing papers in PubMed, 118 citations in OpenAlex.

  1. International journal of molecular sciences · 2026
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  13. Engineering filamentous myosins for optical control of contractility.bioRxiv : the preprint server for biology · 2025
    Article
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  15. Myosin 2 - A general contractor for the cytoskeleton.Current opinion in cell biology · 2025
    Review
  16. Reduced cell-substrate adhesion formation promotes cell migration inbioRxiv : the preprint server for biology · 2025
    Article
  17. Article
  18. Review
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18 more citing papers are in PubMed but not listed here.

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

5 authors at 1 institution in 1 country.

Jonathan D WinkelmanInstitute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637; jon.winkelman@gmail.com drkovar@uchicago.edu gardel@uchicago.edu.ORCID 0000-0002-8870-2917
Caitlin A AndersonDepartment of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637.ORCID 0000-0003-4688-2371
Cristian SuarezDepartment of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637.ORCID 0000-0001-8279-3515
David R KovarDepartment of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637; jon.winkelman@gmail.com drkovar@uchicago.edu gardel@uchicago.edu.
Margaret L GardelInstitute for Biophysical Dynamics, University of Chicago, Chicago, IL 60637; jon.winkelman@gmail.com drkovar@uchicago.edu gardel@uchicago.edu.
University of Chicago · US

Funding

Mechanisms of Formin-Mediated Actin Filament Assembly - Renewal 01 - ResubmissionR01GM079265 · NIGMS · UNIVERSITY OF CHICAGO · PI KOVAR, DAVID R · 2007 to 2023
$4.5M
Mechanical Regulation of Cell Adhesion by Dynamic Cytoskeletal Assemblies - Resubmission 01R01GM104032 · NIGMS · UNIVERSITY OF CHICAGO · PI GARDEL, MARGARET LISE · 2015 to 2023
$2.5M
Functional Reconstitution of Yeast ExocytosisR01GM071832 · NIGMS · RICE UNIVERSITY · PI MCNEW, JAMES A · 2006 to 2010
$1.4M
Mechanosensing in LIM Domain ProteinsF32GM122372 · NIGMS · UNIVERSITY OF CHICAGO · PI WINKELMAN, JONATHAN DAVID · 2017 to 2019
$179k
NIGMS NIH HHS F32 GM122372NIGMS NIH HHS R01 GM071832NIGMS NIH HHS R01 GM079265NIGMS NIH HHS R01 GM104032
6 · The paper itself

Abstract

The actin cytoskeleton assembles into diverse load-bearing networks, including stress fibers (SFs), muscle sarcomeres, and the cytokinetic ring to both generate and sense mechanical forces. The LIM (Lin11, Isl- 1, and Mec-3) domain family is functionally diverse, but most members can associate with the actin cytoskeleton with apparent force sensitivity. Zyxin rapidly localizes via its LIM domains to failing SFs in cells, known as strain sites, to initiate SF repair and maintain mechanical homeostasis. The mechanism by which these LIM domains associate with stress fiber strain sites (SFSS) is not known. Additionally, it is unknown how widespread strain sensing is within the LIM protein family. We identify that the LIM domain-containing region of 18 proteins from the Zyxin, Paxillin, Tes, and Enigma proteins accumulate to SFSS. Moreover, the LIM domain region from the fission yeast protein paxillin like 1 (Pxl1) also localizes to SFSS in mammalian cells, suggesting that the strain sensing mechanism is ancient and highly conserved. We then used sequence and domain analysis to demonstrate that tandem LIM domains contribute additively, for SFSS localization. Employing in vitro reconstitution, we show that the LIM domain-containing region from mammalian zyxin and fission yeast Pxl1 binds to mechanically stressed F-actin networks but does not associate with relaxed actin filaments. We propose that tandem LIM domains recognize an F-actin conformation that is rare in the relaxed state but is enriched in the presence of mechanical stress.

Indexed as

Amino Acid SequenceAnimalsBiomechanical PhenomenaCell LineConserved SequenceEvolution, MolecularLIM Domain ProteinsMiceMyosinsProtein BindingStress FibersStress, MechanicalYeastsLIM Domain ProteinsMyosinsactin cytoskeletoncell mechanosensingmyosin

Identifiers

PMID32989126
PMCPMC7568268
OpenAlexW3089477642

What Socratic holds

Textmetadata
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 Socratic graph.