Project description: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.
Project description:The amount of RNA sequencing data on skeletal muscle is very limited. We have analyzed a large set of human muscle biopsy samples and provide extensive information on the baseline skeletal muscle transcriptome, including completely novel protein-coding transcripts. Analyze of transcriptome in 24 skeletal muscle biopsy samples, 12 individuals and one biopsy per leg per individual. This experiment is linked to E-GEOD-58387.
Project description:The goal of this study is to characterize the genetic changes that occur in muscle of mice carrying a mutant allele for STIM1 (D84G)
Project description:The amount of RNA sequencing data on skeletal muscle is very limited. We have analyzed a large set of human muscle biopsy samples and provide extensive information on the baseline skeletal muscle transcriptome, including completely novel protein-coding transcripts.