Evidence map›Paper›PMID 15247427›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2004

NFAT is a nerve activity sensor in skeletal muscle and controls activity-dependent myosin switching.

Karl J A McCullagh, Elisa Calabria, Giorgia Pallafacchina, Stefano Ciciliot, Antonio L Serrano, Carla Argentini, John M Kalhovde, Terje Lømo, Stefano Schiaffino

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 105 papers.

0numbers the graph read from it
0cells of the map it votes in
105citing papers in PubMed
5.8field-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

105 citing papers in PubMed, 219 citations in OpenAlex.

  1. Ets2 Is an Activity-Dependent Transcriptional Regulator of a Fast-Twitch Muscle Program.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Article
  2. Review
  3. Review
  4. Article
  5. Review of the Pathology of Muscle in Amyotrophic Lateral Sclerosis.International journal of molecular sciences · 2026
    Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Muscle Plasticity, Adaptation and Epigenetics.Advances in experimental medicine and biology · 2025
    Review
  13. Review
  14. Review
  15. Review
  16. Article
  17. Developmental, physiologic and phylogenetic perspectives on the expression and regulation of myosin heavy chains in mammalian skeletal muscles.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2023
    Review
  18. Article
  19. Article
  20. Article

45 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Karl J A McCullaghDepartment of Biomedical Sciences, Consiglio Nazionale delle Ricerche Institute of Neurosciences, University of Padua, 35121 Padua, Italy.
Elisa Calabria
Giorgia Pallafacchina
Stefano Ciciliot
Antonio L Serrano
Carla Argentini
John M Kalhovde
Terje Lømo
Stefano Schiaffino
University of Padua · ITVeneto Institute of Molecular Medicine · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Calcineurin (Cn) signaling has been implicated in nerve activity-dependent fiber type specification in skeletal muscle, but the downstream effector pathway has not been established. We have investigated the role of the transcription factor nuclear factor of activated T cells (NFAT), a major target of Cn, by using an in vivo transfection approach in regenerating and adult rat muscles. NFAT transcriptional activity was monitored with two different NFAT-dependent reporters and was found to be higher in slow compared to fast muscles. NFAT activity is decreased by denervation in slow muscles and is increased by electrostimulation of denervated muscles with a tonic low-frequency impulse pattern, mimicking the firing pattern of slow motor neurons, but not with a phasic high-frequency pattern typical of fast motor neurons. To determine the role of NFAT, we transfected regenerating and adult rat muscles with a plasmid coding for VIVIT, a specific peptide inhibitor of Cn-mediated NFAT activation. VIVIT was found to block the expression of slow myosin heavy chain (MyHC-slow) induced by slow motor neuron activity in regenerating slow soleus muscle and to inhibit the expression of MyHC-slow transcripts and the activity of a MyHC-slow promoter in adult soleus. The role of NFAT was confirmed by the finding that a constitutively active NFATc1 mutant stimulates the MyHC-slow, inhibits the fast MyHC-2B promoter in adult fast muscles, and induces MyHC-slow expression in regenerating muscles. These results support the notion that Cn-NFAT signaling acts as a nerve activity sensor in skeletal muscle in vivo and controls nerve activity-dependent myosin switching.

Indexed as

Gene Expression RegulationNuclear ProteinsAnimalsCalcineurinDNA-Binding ProteinsElectric StimulationGenes, ReporterIn Vitro TechniquesMaleMotor NeuronsMuscle Fibers, Fast-TwitchMuscle Fibers, Slow-TwitchMuscle, SkeletalMyosinsNFATC Transcription FactorsOligopeptidesCalcineurinDNA-Binding ProteinsMyosinsNFATC Transcription FactorsNuclear ProteinsOligopeptidesRecombinant Fusion ProteinsTranscription FactorsVIVIT peptide

Identifiers

PMID15247427
PMCPMC489979
OpenAlexW2043445408

What OpenQuestion 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 OpenQuestion graph.