Evidence map›Paper›PMID 38769542›Full record

ArticleSkeletal muscle2024

CaMKIIβ deregulation contributes to neuromuscular junction destabilization in Myotonic Dystrophy type I.

Denis Falcetta, Sandrine Quirim, Ilaria Cocchiararo, Florent Chabry, Marine Théodore, Adeline Stiefvater, Shuo Lin, Lionel Tintignac, Robert Ivanek, Jochen Kinter and 3 more

Abstract read
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In one paragraph

Article in Skeletal muscle, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Article
  2. HSAInternational journal of molecular sciences · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. 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

13 authors.

Denis FalcettaDepartment of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1 rue Michel Servet, Geneva, CH-1211, Switzerland.
Sandrine QuirimDepartment of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1 rue Michel Servet, Geneva, CH-1211, Switzerland.
Ilaria CocchiararoDepartment of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1 rue Michel Servet, Geneva, CH-1211, Switzerland.
Florent ChabryDepartment of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1 rue Michel Servet, Geneva, CH-1211, Switzerland.
Marine ThéodoreNeuromuscular Research Group, Departments of Neurology and Biomedicine, University and University Hospital Basel, Klingelbergstrasse 50/70, Basel, CH-4056, Switzerland.
Adeline StiefvaterNeuromuscular Research Group, Departments of Neurology and Biomedicine, University and University Hospital Basel, Klingelbergstrasse 50/70, Basel, CH-4056, Switzerland.
Shuo LinBiozentrum, University of Basel, Spitalstrasse 41, Basel, CH-4056, Switzerland.
Lionel TintignacNeuromuscular Research Group, Departments of Neurology and Biomedicine, University and University Hospital Basel, Klingelbergstrasse 50/70, Basel, CH-4056, Switzerland.
Robert IvanekDepartment of Biomedicine, University Hospital and University of Basel, Hebelstrasse 20, Basel, CH-4053, Switzerland.
Jochen KinterNeuromuscular Research Group, Departments of Neurology and Biomedicine, University and University Hospital Basel, Klingelbergstrasse 50/70, Basel, CH-4056, Switzerland.
Markus A RüeggBiozentrum, University of Basel, Spitalstrasse 41, Basel, CH-4056, Switzerland.
Michael SinnreichNeuromuscular Research Group, Departments of Neurology and Biomedicine, University and University Hospital Basel, Klingelbergstrasse 50/70, Basel, CH-4056, Switzerland.
Perrine CastetsDepartment of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1 rue Michel Servet, Geneva, CH-1211, Switzerland. perrine.castets@unige.ch.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMyotonic Dystrophy type I (DM1) is the most common muscular dystrophy in adults. Previous reports have highlighted that neuromuscular junctions (NMJs) deteriorate in skeletal muscle from DM1 patients and mouse models thereof. However, the underlying pathomechanisms and their contribution to muscle dysfunction remain unknown.

methodsWe compared changes in NMJs and activity-dependent signalling pathways in HSA

resultsMuscle from DM1 mouse models showed major deregulation of calcium/calmodulin-dependent protein kinases II (CaMKIIs), which are key activity sensors regulating synaptic gene expression and acetylcholine receptor (AChR) recycling at the NMJ. Both mouse models exhibited increased fragmentation of the endplate, which preceded muscle degeneration. Endplate fragmentation was not accompanied by changes in AChR turnover at the NMJ. However, the expression of synaptic genes was up-regulated in mutant innervated muscle, together with an abnormal accumulation of histone deacetylase 4 (HDAC4), a known target of CaMKII. Interestingly, denervation-induced increase in synaptic gene expression and AChR turnover was hampered in DM1 muscle. Importantly, CaMKIIβ/βM overexpression normalized endplate fragmentation and synaptic gene expression in innervated Mbnl1

conclusionsOur results indicate that CaMKIIβ-dependent and -independent mechanisms perturb synaptic gene regulation and muscle response to denervation in DM1 mouse models. Changes in these signalling pathways may contribute to NMJ destabilization and muscle dysfunction in DM1 patients.

Indexed as

Calcium-Calmodulin-Dependent Protein Kinase Type 2Disease Models, AnimalMuscle, SkeletalMyotonic DystrophyNeuromuscular JunctionAnimalsHistone DeacetylasesHumansMaleMiceMice, Inbred C57BLReceptors, CholinergicCalcium-Calmodulin-Dependent Protein Kinase Type 2Camk2b protein, mouseHdac5 protein, mouseHistone DeacetylasesReceptors, CholinergicCaMKIIFibre typeMyotonic dystrophyNeuromuscular junctionsSynaptic genes

Identifiers

PMID38769542
PMCPMC11106974

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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.