Evidence map›Paper›PMID 40663059›Full record

ArticleeLife2025

Human formin FHOD3-mediated actin elongation is required for sarcomere integrity in cardiomyocytes.

Dylan A Valencia, Angela N Koeberlein, Haruko Nakano, Akos Rudas, Aanand A Patel, Airi Harui, Cassandra Spencer, Atsushi Nakano, Margot E Quinlan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in eLife, 2025. 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. Review
  2. Hypertrophic Cardiomyopathy is a Disease of Sarcomere Proteins.Methodist DeBakey cardiovascular journal · 2026
    Review
  3. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors.

Dylan A ValenciaDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, United States.ORCID https://orcid.org/0000-0003-1503-5081
Angela N KoeberleinDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, United States.
Haruko NakanoDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.ORCID https://orcid.org/0000-0001-5807-9127
Akos RudasDepartment of Computational Medicine, University of California, Los Angeles, Los Angeles, United States.
Aanand A PatelDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, United States.ORCID https://orcid.org/0000-0002-1509-9950
Airi HaruiDepartment of Medicine, Divison of Pulmonary and Critical Care Medicine, Geffen School of Medicine, University of California, Los Angeles, Los Angeles, United States.ORCID https://orcid.org/0000-0002-5730-4035
Cassandra SpencerDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.
Atsushi NakanoDepartment of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, United States.ORCID https://orcid.org/0000-0001-5702-5039
Margot E QuinlanDepartment of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, United States.ORCID https://orcid.org/0000-0002-8133-1033

Funding

UCLA NIGMS T32 Program AssessmentT32GM007185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TORRES, JORGE · 1985 to 2020
$21.7M
Muscle Cell Biology, Pathophysiology, and TherapeuticsT32AR065972 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Rachelle Hope Crosbie, THOMAS A. RANDO · 2016 to 2026
$3.9M
Using formins to build distinct structures in cardiomyocytesR01HL146159 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI QUINLAN, MARGOT E · 2019 to 2022
$1.5M
Multiphoton Microscope for Deep Tissue ImagingS10OD025017 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BENTOLILA, LAURENT A. · 2018 to 2018
$599k
NHLBI NIH HHS R01 HL146159NIAMS NIH HHS T32 AR065972NIGMS NIH HHS T32 GM007185NIH HHS R01 HL146159NIH HHS S10 OD025017NIH HHS T32 AR065972NIH HHS T32 GM007185
6 · The paper itself

Abstract

Contractility and cell motility depend on accurately controlled assembly of the actin cytoskeleton. Formins are a large group of actin assembly proteins that nucleate and elongate new actin filaments. Some formins may cap filaments while others sever or bundle filaments. The formin homology domain-containing protein (FHOD) family of formins is critical to the formation of the fundamental contractile unit in muscle, the sarcomere. Specifically, mammalian FHOD3L plays an essential role in cardiomyocytes. Despite our knowledge of FHOD3L's importance in cardiomyocytes, its biochemical and cellular activities remain poorly understood. It was proposed that FHOD-family formins act by capping and bundling, as opposed to assembling new filaments. Here, we demonstrate that human FHOD3L nucleates actin and rapidly but briefly elongates filaments after temporarily pausing elongation. We designed function-separating mutants that enabled us to distinguish which biochemical roles are required in the cell. We found that FHOD3L's elongation activity, but not its nucleation, capping, or bundling activity, is necessary for proper sarcomere formation and contractile function in neonatal rat ventricular myocytes. The results of this work provide new insight into the mechanisms by which formins build specific structures and will contribute to knowledge regarding how cardiomyopathies arise from defects in sarcomere formation and maintenance.

Indexed as

ActinsForminsMicrofilament ProteinsMyocytes, CardiacSarcomeresActin CytoskeletonAnimalsCells, CulturedHumansRatsActinsFHOD3 protein, humanForminsMicrofilament Proteinsactincell biologydevelopmental biologyhearthypertrophic cardiomyopathyrat

Identifiers

PMID40663059
PMCPMC12263155

What OpenQuestion holds

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LicenceCC BY
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.