Exercise-dependent formation of new junctions that promote STIM1-Orai1 assembly in skeletal muscle

Scientific Reports
Simona BoncompagniFeliciano Protasi

Abstract

Store-operated Ca2+ entry (SOCE), a ubiquitous mechanism that allows recovery of Ca2+ ions from the extracellular space, has been proposed to limit fatigue during repetitive skeletal muscle activity. However, the subcellular location for SOCE in muscle fibers has not been unequivocally identified. Here we show that exercise drives a significant remodeling of the sarcotubular system to form previously unidentified junctions between the sarcoplasmic reticulum (SR) and transverse-tubules (TTs). We also demonstrate that these new SR-TT junctions contain the molecular machinery that mediate SOCE: stromal interaction molecule-1 (STIM1), which functions as the SR Ca2+ sensor, and Orai1, the Ca2+-permeable channel in the TT. In addition, EDL muscles isolated from exercised mice exhibit an increased capability of maintaining contractile force during repetitive stimulation in the presence of 2.5 mM extracellular Ca2+, compared to muscles from control mice. This functional difference is significantly reduced by either replacement of extracellular Ca2+ with Mg2+ or the addition of SOCE inhibitors (BTP-2 and 2-APB). We propose that the new SR-TT junctions formed during exercise, and that contain STIM1 and Orai1, function as Ca 2+ Entry Unit...Continue Reading

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Citations

Oct 29, 2019·ELife·Antonio MichelucciFeliciano Protasi
Aug 20, 2020·Journal of Muscle Research and Cell Motility·Feliciano ProtasiSimona Boncompagni
Aug 28, 2020·The Journal of General Physiology·Werner Melzer
Aug 8, 2020·The Journal of General Physiology·Antonio MichelucciRobert T Dirksen
Jun 4, 2020·Journal of Muscle Research and Cell Motility·Daniela RossiVincenzo Sorrentino
Oct 20, 2020·Neuropathology : Official Journal of the Japanese Society of Neuropathology·Georges Arielle PecheJohann Böhm
Nov 13, 2020·Acta Neuropathologica Communications·Laurent PelletierIsabelle Marty
Feb 28, 2021·Pflügers Archiv : European journal of physiology·Paul RosenbergChaojian Wang
Feb 24, 2020·Current Opinion in Cell Biology·Christopher J Stefan
Jun 24, 2020·Cell Calcium·Qian Wang, Marek Michalak
May 7, 2021·Skeletal Muscle·Jessica BrunettiMaud Frieden
May 13, 2021·The Journal of General Physiology·Muhammad S Khan, Robin M Shaw
Jul 3, 2021·International Journal of Molecular Sciences·Feliciano ProtasiSimona Boncompagni
Dec 16, 2021·The Journal of General Physiology·Lan Wei-LaPierreRobert T Dirksen

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Methods Mentioned

BETA
electron microscopy
confocal microscopy

Software Mentioned

Analy
SIS
Imaris
LSM
Zeiss

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