RGD Reference Report - Acute Skeletal Muscle Contractions Orchestrate Signaling Mechanisms to Trigger Nuclear NFATc1 Shuttling and Epigenetic Histone Modifications. - Rat Genome Database

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Acute Skeletal Muscle Contractions Orchestrate Signaling Mechanisms to Trigger Nuclear NFATc1 Shuttling and Epigenetic Histone Modifications.

Authors: Suhr, Frank  Braun, Kristina  Vanmunster, Matthias  Bloch, Wilhelm 
Citation: Suhr F, etal., Cell Physiol Biochem. 2019;52(3):633-652. doi: 10.33594/000000045.
RGD ID: 329337341
Pubmed: PMID:30907990   (View Abstract at PubMed)
DOI: DOI:10.33594/000000045   (Journal Full-text)


BACKGROUND/AIMS: Calcium (Ca²⁺) coordinates skeletal muscle functions by controlling contractions as well as signaling pathways and transcriptional properties. The ryanodine receptor 1 (RyR1), its phosphorylation site (pRyR1Ser²⁸⁴⁰) and its stabilizers navigate Ca²⁺ oscillations to command muscle signaling cascades and transcriptional activities. While chronic exercise increases pRyR1Ser²⁸⁴⁰, investigations on acute exercise's effects on RyR1 and Ca²⁺-dependent modifications of skeletal muscle are rare. The aim of this study was to examine molecular events leading to RyR1 phosphorylation in a physiological model of acute exercise. We hypothesized that exercise-induced RyR1 phosphorylation is associated with altered Ca²⁺-dependent physiological phenotypes.
METHODS: We analyzed pRyR1Ser²⁸⁴⁰, its stabilizers, involved signaling pathways, and Ca²⁺-sensitive muscle-determining factors (i.e. NFATc1 and epigenetic histone H3 modifications) in rat muscles upon one single running bout of either concentric or eccentric contractions.
RESULTS: Both acute exercises significantly increased pRyRSer²⁸⁴⁰ levels in muscles, which was accompanied by dissociations of stabilizers from RyR1. Additionally, RyR1 phosphorylation-inducing signaling cascades PTEN/CaMKII/ PKA were significantly activated upon exercise. Further, RyR1 phosphorylations were associated with increased Ca²⁺-dependent NFATc1 nuclear abundances as well as increased Ca²⁺-dependent epigenetic H3 acetylations pointing to a pRyR1Ser²⁸⁴⁰-dependent rapid and novel Ca²⁺ equilibrium upon exercise.
CONCLUSION: Our data report synergistic actions of several distinct pathways to modify RyR1 function to govern physiological phenotypes, here expressed as increased nuclear NFATc1 abundances and epigenetic H3 modifications.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to muscle activity  IEP 329337341; 329337341 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
sarcoplasm  IDA 329337341MMO:0000679RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nfatc1  (nuclear factor of activated T-cells 1)
Ryr1  (ryanodine receptor 1)


Additional Information