Dataset Information

Disruption of STIM1-mediated Ca2+ sensing and energy metabolism in adult skeletal muscle compromises exercise tolerance, proteostasis and lean mass

ABSTRACT: STIM1 is a single-pass transmembrane endoplasmic/sarcoplasmic reticulum (E/SR) protein recognized for its role in store operated Ca2+ entry (SOCE), an ancient and ubiquitous signaling pathway. Whereas STIM1 is indispensable during development, its biological and metabolic functions in mature muscle were unclear. Shown here, STIM1 is abundant in adult skeletal muscle, upregulated by exercise, and present at SR-mitochondria interfaces. Among its multifaceted roles, STIM1 regulates Ca2+ signaling, mitochondrial Ca2+ loading, energy metabolism and protein homeostasis. Thus, inducible tissue-specific deletion of STIM1 (iSTIM1 KO) in adult muscle leads to diminished lean mass, reduced exercise capacity, and perturbed fuel selection in settings of energetic stress, without affecting whole-body glucose tolerance. Proteomics and phospho-proteomics analyses of iSTIM1 KO muscles revealed molecular signatures of low-grade E/SR stress and broad activation of processes and signaling networks involved in proteostasis. The findings provide insight into the pathophysiology of muscle diseases linked to disturbances in STIM1-dependent calcium handling.

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Deborah Muoio

PROVIDER: PXD030674 | JPOST Repository | Thu Dec 30 00:00:00 GMT 2021

REPOSITORIES: jPOST

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			Action	DRS
	2021-01-26_Muoio_BeckyWilson_STIM1-SKM_TMT10_PhosphoF1_Run1.raw	Raw
	2021-01-26_Muoio_BeckyWilson_STIM1-SKM_TMT10_PhosphoF1_Run2.raw	Raw
	2021-01-26_Muoio_BeckyWilson_STIM1-SKM_TMT10_PhosphoF1_Run3.raw	Raw
	2021-01-26_Muoio_BeckyWilson_STIM1-SKM_TMT10_PhosphoF2_Run1.raw	Raw
	2021-01-26_Muoio_BeckyWilson_STIM1-SKM_TMT10_PhosphoF2_Run2.raw	Raw

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Publications

Disruption of STIM1-mediated Ca<sup>2+</sup> sensing and energy metabolism in adult skeletal muscle compromises exercise tolerance, proteostasis, and lean mass.

Wilson Rebecca J RJ Lyons Scott P SP Koves Timothy R TR Bryson Victoria G VG Zhang Hengtao H Li TianYu T Crown Scott B SB Ding Jin-Dong JD Grimsrud Paul A PA Rosenberg Paul B PB Muoio Deborah M DM

Molecular metabolism 20211231

<h4>Objective</h4>Stromal interaction molecule 1 (STIM1) is a single-pass transmembrane endoplasmic/sarcoplasmic reticulum (E/SR) protein recognized for its role in a store operated Ca<sup>2+</sup> entry (SOCE), an ancient and ubiquitous signaling pathway. Whereas STIM1 is known to be indispensable during development, its biological and metabolic functions in mature muscles remain unclear.<h4>Methods</h4>Conditional and tamoxifen inducible muscle STIM1 knock-out mouse models were coupled with mu ...[more]

PMID: 34979330

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