Evidence map›Paper›PMID 41641537›Full record

ArticleCirculation research2026

N-Terminal Actin-Binding Site of Lmod2 Promotes Controlled Pointed End Elongation.

Tania M Larrinaga, Garry E Smith, Dmitri Tolkatchev, Timothy J Rast, Thomas A Bunch, Brett A Colson, Christopher T Pappas, Alla S Kostyukova, Carol C Gregorio

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In one paragraph

Article in Circulation research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
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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

9 authors.

Tania M Larrinaga *Department of Cellular and Molecular Medicine and Sarver Molecular Cardiovascular Research Program, The University of Arizona, Tucson (T.M.L., T.J.R., T.A.B., B.A.C., C.T.P., C.C.G.).ORCID 0000-0002-4091-1808
Garry E Smith *Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman (G.E.S., D.T., A.S.K.).
Dmitri TolkatchevVoiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman (G.E.S., D.T., A.S.K.).ORCID 0000-0002-1300-6458
Timothy J RastDepartment of Cellular and Molecular Medicine and Sarver Molecular Cardiovascular Research Program, The University of Arizona, Tucson (T.M.L., T.J.R., T.A.B., B.A.C., C.T.P., C.C.G.).
Thomas A BunchORCID 0000-0002-6237-1427
Brett A ColsonDepartment of Cellular and Molecular Medicine and Sarver Molecular Cardiovascular Research Program, The University of Arizona, Tucson (T.M.L., T.J.R., T.A.B., B.A.C., C.T.P., C.C.G.).ORCID 0000-0002-5721-4320
Christopher T PappasDepartment of Cellular and Molecular Medicine and Sarver Molecular Cardiovascular Research Program, The University of Arizona, Tucson (T.M.L., T.J.R., T.A.B., B.A.C., C.T.P., C.C.G.).
Alla S Kostyukova *Voiland School of Chemical Engineering and Bioengineering, Washington State University, Pullman (G.E.S., D.T., A.S.K.).
Carol C Gregorio *Department of Cellular and Molecular Medicine and Sarver Molecular Cardiovascular Research Program, The University of Arizona, Tucson (T.M.L., T.J.R., T.A.B., B.A.C., C.T.P., C.C.G.).

Funding

Deciphering the role of Lmod2 in thin filament length regulation and dilated cardiomyopathyR01HL123078 · NHLBI · UNIVERSITY OF ARIZONA · PI Carol C Gregorio, Shashank Shekhar · 2015 to 2026
$5.6M
REGULATION OF THE ACTIN FILAMENT POINTED END DYNAMICS IN HEALTH AND DISEASER01GM120137 · NIGMS · WASHINGTON STATE UNIVERSITY · PI GALKIN, VITOLD, GREGORIO, CAROL C · 2017 to 2024
$4.0M
Deciphering the roles of FXR1 in health and myopathyR01HL164644 · NHLBI · UNIVERSITY OF ARIZONA · PI GREGORIO, CAROL C · 2022 to 2025
$2.5M
Regulation of thin filament architecture by CAP2 in health and myopathyR01HL173431 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Carol C Gregorio · 2025 to 2026
$1.4M
NHLBI NIH HHS R01 HL123078NHLBI NIH HHS R01 HL164644NHLBI NIH HHS R01 HL173431NIGMS NIH HHS R01 GM120137
6 · The paper itself

Abstract

backgroundLmods (leiomodins) are critical for the assembly and maintenance of thin filaments in striated muscles by allowing thin filament elongation at the pointed ends. Lmod2's elongation function has been linked to both actin-binding sites (ABSs) 2 and 3, while the existence and function of an N-terminal ABS1 has been debated.

methodsTo elucidate the little-known role of Lmod2's ABS1, we created a mutant (F64D/L69D/W72D/W73D: Lmod2-quadruple mutant) predicted to decrease the binding of ABS1 to actin. We analyzed the effect of the mutations using several in vitro, cellular, and in vivo assays.

resultsBy disrupting the interaction of Lmod2 ABS1 with actin in isolated cardiomyocytes and in mice, we engineered a super Lmod2 that results in remarkably longer thin filaments. Structural analysis determined that ABS1 of Lmod2 binds to actin through a disordered region and an amphipathic α-helix. Analysis of the mutated ABS1 revealed that the helix is destroyed, and binding to actin is maintained only in the N-terminal disordered region of Lmod2 ABS1.

conclusionsThese discoveries support a model of controlled thin filament pointed end elongation by Lmod2 and provide the first direct evidence of, as well as the structural and functional mechanistic basis for, Lmod2's physiological leaky cap activity.

Indexed as

actinscardiomyopathy, dilatedmicroscopymuscle contractionsarcomeres

Identifiers

PMID41641537
PMCPMC13178850

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Registered trials

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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.