Evidence map›Paper›PMID 42717863›Full record

ArticleCirculation research2026

Nx3 Is a Z-Disk Structural and Signaling Hub That Is Reduced in Heart Failure.

Wolfgang A Linke, Lisa Kümper, Andrey Fomin, Isabel Martin, Nadezda Ignatyeva, Ken Hashimoto, Clemens G Mohr, Josefine Bässler, Anna Gärtner, Momoko Ohira and 22 more

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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 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
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

32 authors.

Wolfgang A LinkeInstitute of Physiology II (W.A.L., A.F., C.G.M., J.B., A.J.K., J.K.F., A. Hucke, F.K., A.U.), University Hospital Münster, Germany.ORCID 0000-0003-0801-3773
Lisa KümperInstitute of Physiology, Ruhr-University Bochum, Germany (L.K., K.S., T.V.).
Andrey FominInstitute of Physiology II (W.A.L., A.F., C.G.M., J.B., A.J.K., J.K.F., A. Hucke, F.K., A.U.), University Hospital Münster, Germany.ORCID 0000-0001-5578-6977
Isabel MartinDepartment of Biology (I.M., O.M.), University of Konstanz, Germany.ORCID 0009-0007-4172-3204
Nadezda IgnatyevaDepartment of Cardiology and Pneumology, University Medical Center Göttingen, Germany (W.A.L., A.F., N.I., A.E.).ORCID 0009-0008-4421-0495
Ken HashimotoFirst Department of Physiology, Kawasaki Medical School, Okayama, Japan (K.H., M.O., A. Hanashima, S.M.).ORCID 0000-0001-6194-9971
Clemens G MohrInstitute of Physiology II (W.A.L., A.F., C.G.M., J.B., A.J.K., J.K.F., A. Hucke, F.K., A.U.), University Hospital Münster, Germany.ORCID 0009-0005-7708-3005
Josefine BässlerInstitute of Physiology II (W.A.L., A.F., C.G.M., J.B., A.J.K., J.K.F., A. Hucke, F.K., A.U.), University Hospital Münster, Germany.
Anna GärtnerErich and Hanna Klessmann Institute, Heart and Diabetes Centre NRW, University Hospital of the Ruhr-University Bochum, Bad Oeynhausen, Germany (A.G., J.F.G., H.M.).ORCID 0000-0001-6899-7693
Momoko OhiraFirst Department of Physiology, Kawasaki Medical School, Okayama, Japan (K.H., M.O., A. Hanashima, S.M.).
Akira HanashimaFirst Department of Physiology, Kawasaki Medical School, Okayama, Japan (K.H., M.O., A. Hanashima, S.M.).ORCID 0000-0002-0232-6421
Annika J KlotzInstitute of Physiology II (W.A.L., A.F., C.G.M., J.B., A.J.K., J.K.F., A. Hucke, F.K., A.U.), University Hospital Münster, Germany.ORCID 0000-0002-4555-2306
Kai SchifferInstitute of Physiology, Ruhr-University Bochum, Germany (L.K., K.S., T.V.).
Tobias VoelkelInstitute of Physiology, Ruhr-University Bochum, Germany (L.K., K.S., T.V.).
Johanna K FreundtInstitute of Physiology II (W.A.L., A.F., C.G.M., J.B., A.J.K., J.K.F., A. Hucke, F.K., A.U.), University Hospital Münster, Germany.ORCID 0009-0009-1356-7624
Anna HuckeInstitute of Physiology II (W.A.L., A.F., C.G.M., J.B., A.J.K., J.K.F., A. Hucke, F.K., A.U.), University Hospital Münster, Germany.
Franziska KoserInstitute of Physiology II (W.A.L., A.F., C.G.M., J.B., A.J.K., J.K.F., A. Hucke, F.K., A.U.), University Hospital Münster, Germany.ORCID 0009-0008-9585-0935
Tao ZhangInstitute of Physical Biology, University of Düsseldorf, Germany (T.Z.).ORCID 0000-0002-8157-7674
Anastasia J HobbachDepartment of Cardiology I, Coronary, Peripheral Vascular Disease and Heart Failure (A.J.H.), University Hospital Münster, Germany.ORCID 0000-0001-6421-8429
Ian A GlassBirth Defects Research Laboratory, Department of Pediatrics (I.A.G.), University of Washington, Seattle.ORCID 0000-0001-6762-8407
Birth Defects Research Laboratory
Jan F GummertErich and Hanna Klessmann Institute, Heart and Diabetes Centre NRW, University Hospital of the Ruhr-University Bochum, Bad Oeynhausen, Germany (A.G., J.F.G., H.M.).ORCID 0000-0002-6956-9110
Cristobal G Dos RemediosVictor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia (C.G.d.R.).ORCID 0000-0003-1052-7490
Sebastiaan van HeeschPrincess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands (S.v.H.).ORCID 0000-0001-9593-1980
Jorge Ruiz-OreraCardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany (J.R.-O., N.H.).ORCID 0000-0002-8317-0034
Satoshi MohriFirst Department of Physiology, Kawasaki Medical School, Okayama, Japan (K.H., M.O., A. Hanashima, S.M.).
Norbert HubnerCardiovascular and Metabolic Sciences, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany (J.R.-O., N.H.).
Michael RegnierDepartment of Bioengineering (M.R.), University of Washington, Seattle.ORCID 0000-0001-5437-9851
Hendrik MiltingErich and Hanna Klessmann Institute, Heart and Diabetes Centre NRW, University Hospital of the Ruhr-University Bochum, Bad Oeynhausen, Germany (A.G., J.F.G., H.M.).ORCID 0000-0001-9722-0007
Olga MayansDepartment of Biology (I.M., O.M.), University of Konstanz, Germany.
Andreas UngerInstitute of Physiology II (W.A.L., A.F., C.G.M., J.B., A.J.K., J.K.F., A. Hucke, F.K., A.U.), University Hospital Münster, Germany.
Antje EbertDepartment of Cardiology and Pneumology, University Medical Center Göttingen, Germany (W.A.L., A.F., N.I., A.E.).ORCID 0000-0002-3642-242X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNx3 (novex-3) is an exceptionally small isoform of the giant protein titin, whose structural and functional roles within the sarcomere remain poorly understood.

methodsWe used a comprehensive, multimodal approach to define the key properties of Nx3 in healthy and failing hearts, including its abundance relative to FLT (full-length titin), sarcomeric localization, protein interactions, and functional relevance in mouse and human cardiomyocytes under physiological and pathological conditions. Using Western blotting, quantitative polymerase chain reaction, total RNA sequencing, and ribosome profiling, we show that Nx3 is constitutively expressed from fetal development through adulthood.

resultsIn adult mouse and human myocardium, Nx3 accounts for ≈20% to 25% of total titin protein, despite representing only ≈8% to 14% at the transcript level. Immunoelectron microscopy and binding studies reveal that Nx3 adopts a nonlinear configuration within the sarcomere: its N terminus is anchored at the Z-disk, although the proximal portion of its unique region encoded by

conclusionsNx3 regulates Z-disk stability and modulates signaling pathways that optimize cardiac performance, and its dysregulation contributes to heart failure pathogenesis.

Indexed as

ConnectinHeart FailureMyocytes, CardiacRNA-Binding ProteinsSarcomeresAnimalsFemaleHumansMaleMiceMice, Inbred C57BLProtein KinasesSignal TransductionConnectinProtein KinasesRNA-Binding Proteinstitin protein, mousecardiomyopathiesheart failuremyocardiumsarcomerestitin

Identifiers

PMID42717863
PMCPMC13649281

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