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

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 iden...

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Autores principales:	Simona Boncompagni, Antonio Michelucci, Laura Pietrangelo, Robert T. Dirksen, Feliciano Protasi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Stromal Interaction Molecule 1 (STIM1) Store-operated Ca2+ Entry (SOCE) SOCE Inhibitors Repetitive Muscle Activity Sarcotubular System Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7f36ee9092e449bd8ffc75da82df5767
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spelling	oai:doaj.org-article:7f36ee9092e449bd8ffc75da82df57672021-12-02T11:52:21ZExercise-dependent formation of new junctions that promote STIM1-Orai1 assembly in skeletal muscle10.1038/s41598-017-14134-02045-2322https://doaj.org/article/7f36ee9092e449bd8ffc75da82df57672017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-14134-0https://doaj.org/toc/2045-2322Abstract 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 Units (CEUs), structures that provide a pathway to rapidly recover Ca2+ ions from the extracellular space during repetitive muscle activity.Simona BoncompagniAntonio MichelucciLaura PietrangeloRobert T. DirksenFeliciano ProtasiNature PortfolioarticleStromal Interaction Molecule 1 (STIM1)Store-operated Ca2+ Entry (SOCE)SOCE InhibitorsRepetitive Muscle ActivitySarcotubular SystemMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Stromal Interaction Molecule 1 (STIM1) Store-operated Ca2+ Entry (SOCE) SOCE Inhibitors Repetitive Muscle Activity Sarcotubular System Medicine R Science Q
spellingShingle	Stromal Interaction Molecule 1 (STIM1) Store-operated Ca2+ Entry (SOCE) SOCE Inhibitors Repetitive Muscle Activity Sarcotubular System Medicine R Science Q Simona Boncompagni Antonio Michelucci Laura Pietrangelo Robert T. Dirksen Feliciano Protasi Exercise-dependent formation of new junctions that promote STIM1-Orai1 assembly in skeletal muscle
description	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 Units (CEUs), structures that provide a pathway to rapidly recover Ca2+ ions from the extracellular space during repetitive muscle activity.
format	article
author	Simona Boncompagni Antonio Michelucci Laura Pietrangelo Robert T. Dirksen Feliciano Protasi
author_facet	Simona Boncompagni Antonio Michelucci Laura Pietrangelo Robert T. Dirksen Feliciano Protasi
author_sort	Simona Boncompagni
title	Exercise-dependent formation of new junctions that promote STIM1-Orai1 assembly in skeletal muscle
title_short	Exercise-dependent formation of new junctions that promote STIM1-Orai1 assembly in skeletal muscle
title_full	Exercise-dependent formation of new junctions that promote STIM1-Orai1 assembly in skeletal muscle
title_fullStr	Exercise-dependent formation of new junctions that promote STIM1-Orai1 assembly in skeletal muscle
title_full_unstemmed	Exercise-dependent formation of new junctions that promote STIM1-Orai1 assembly in skeletal muscle
title_sort	exercise-dependent formation of new junctions that promote stim1-orai1 assembly in skeletal muscle
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7f36ee9092e449bd8ffc75da82df5767
work_keys_str_mv	AT simonaboncompagni exercisedependentformationofnewjunctionsthatpromotestim1orai1assemblyinskeletalmuscle AT antoniomichelucci exercisedependentformationofnewjunctionsthatpromotestim1orai1assemblyinskeletalmuscle AT laurapietrangelo exercisedependentformationofnewjunctionsthatpromotestim1orai1assemblyinskeletalmuscle AT roberttdirksen exercisedependentformationofnewjunctionsthatpromotestim1orai1assemblyinskeletalmuscle AT felicianoprotasi exercisedependentformationofnewjunctionsthatpromotestim1orai1assemblyinskeletalmuscle
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Exercise-dependent formation of new junctions that promote STIM1-Orai1 assembly in skeletal muscle

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