Ask about this productRelated genes to: STIM1 Blocking Peptide
- Gene:
- STIM1 NIH gene
- Name:
- stromal interaction molecule 1
- Previous symbol:
- -
- Synonyms:
- GOK, D11S4896E
- Chromosome:
- 11p15.4
- Locus Type:
- gene with protein product
- Date approved:
- 1997-02-05
- Date modifiied:
- 2019-04-23
Related products to: STIM1 Blocking Peptide
Related articles to: STIM1 Blocking Peptide
- Heart failure with preserved ejection fraction (HFpEF) arises from chronic cardiometabolic and vascular stress and is increasingly recognized as an inflammatory syndrome with immune dysregulation. Regulatory T cells (Tregs) are critical modulators of cardiovascular inflammation, yet the mechanisms driving Treg dysfunction in HFpEF remain poorly defined. stromal interaction molecule 1 (STIM1)-dependent calcium signaling is a key stress-responsive pathway in immune cells; however, its role in Treg maladaptation during HFpEF remains unknown. - Source: PubMed
Publication date: 2026/07/08
Srinivas BalajiKiran AlluriPeng HongmeiXu JiangFortuno PaulaMay JenniferMoudden Ismail ElRhaleb Nour-EddineHerre John MBenza Raymond LMatrougui Khalid - Tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK) are clinically overlapping disorders characterized by muscle weakness, thrombocytopenia, spleen anomalies and short stature. They are due to mutations affecting the Ca2+ sensor STIM1 or the Ca2+ channel ORAI1 and leading to aberrant Ca2+ homeostasis. Therapeutic approaches aiming to rebalance intracellular Ca2+ levels largely rescued the multi-systemic phenotype in Stim1R304W/+ mice harboring the most common TAM/STRMK mutation. However, the currently used biomarkers to follow disease progression are costly and inadequate for longitudinal studies. Here, we investigated the suitability of MYOM3 to serve as a robust blood-based biomarker for TAM/STRMK. Using only minimal blood volumes, we detected highly elevated circulating MYOM3 levels in plasma samples from Stim1R304W/+ mice and TAM/STRMK patients with different mutations, and we found that the MYOM3 levels were normalized in Stim1R304W/+ mice undergoing efficient therapies. We also identified skeletal muscle as the primary source of circulating MYOM3, a structural protein of the contractile unit in myofibers, and uncovered that MYOM3 is primarily expressed in regenerating muscle fibers and in fast-twitch type IIa fibers. Overall, this work emphasizes the utility of MYOM3 as a minimally-invasive biomarker for disorders involving myofiber degeneration, and highlights the ability of MYOM3 to detect early muscle dysfunction in TAM/STRMK and evaluate therapeutic efficiency. - Source: PubMed
Lafabrie EmmaTard CélineCintas PascalRibes AgnèsLaporte JocelynBöhm Johann - Precise regulation of intracellular calcium signaling is essential for neuronal function and depends on tightly coordinated molecular mechanisms. Among them, endoplasmic reticulum-plasma membrane (ER-PM) junctions form dynamic signaling microdomains that support store-operated calcium entry (SOCE), lipid transfer, phosphoinositide signaling, and ion channel regulation. Within this context, stromal interaction molecules STIM1 and STIM2 act as ER calcium sensors with distinct activation properties. STIM1 is recruited during substantial ER calcium depletion and strong neuronal activity, whereas STIM2 responds to subtle calcium fluctuations and supports basal calcium homeostasis. Upon ER calcium depletion, STIM proteins undergo conformational rearrangement, oligomerization, and translocation to ER-PM junctions, where they engage Orai calcium channels to trigger calcium influx and restore ER calcium balance. Although originally characterized in non-excitable cells, the STIM-Orai signaling axis is now recognized as an important regulator of neuronal calcium dynamics. This system exhibits considerable molecular diversity, with multiple STIM and Orai isoforms and splice variants differing in activation thresholds, subcellular localization, and signaling properties. Consequently, neuronal SOCE is not a uniform calcium entry pathway but contributes to specialized functions across dendrites, dendritic spines, and presynaptic compartments. Beyond classical SOCE, STIM proteins also function as multifunctional organizers of ER architecture and ER-PM junctions, linking calcium homeostasis to dendritic spine morphology, receptor trafficking, neurotransmitter release, and synaptic plasticity. Despite significant progress in this field, a comprehensive comparative understanding of the isoform-specific roles of STIM and Orai proteins in neuronal compartments remains limited. This review summarizes current knowledge regarding the functions of STIM1, STIM2, and Orai1-3 in dendrites and synapses, emphasizing their distinct contributions to calcium homeostasis, local signaling microdomains, and activity-dependent versus homeostatic forms of synaptic plasticity. By integrating evidence from genetic, biochemical, and in vivo studies, this review further highlights region-specific and context-dependent effects, unresolved controversies regarding the physiological roles of STIM and Orai, and the consequences of their dysregulation for neuronal function. - Source: PubMed
Publication date: 2026/07/02
Gruszczynska-Biegala Joanna - Lysosomal two-pore channels (TPC) trigger Ca release from the endoplasmic reticulum (ER). The ensuing ER Ca depletion activates STIM1-gated store-operated Ca entry (SOCE) channels that sustain Ca signals regulating fundamental cellular processes. How TPC channels and STIM1 integrate distinct intra and extracellular cues is unclear. Here, we show that TPC2 activation inhibits SOCE by enforcing rapid and persistent Ca-CaM-dependent inactivation of the STIM-Orai activating region (SOAR). The TPC2 activators NAADP and TPC2-A1-N abrogated SOCE in multiple cell lines and enhanced the slow Ca dependent inactivation (SCDI) of STIM1-gated Orai1 channels. TPC2 engagement triggered lysosomal Ca release and mobilized ER Ca stores but prevented RFP-STIM1 recruitment to the TIRF plane by thapsigargin and disassembled RFP-STIM1 clusters forming after store depletion, preventing and acutely reversing SOCE. These effects persisted in STIM1 mutants truncated after the SOAR and were prevented by TPC2 genetic or pharmacological invalidation, Calmodulin (CaM) inhibition, and cytosolic Ca chelation. We conclude that Ca ions released by TPC2 channels on lysosomes regulate CaM-dependent STIM1 inactivation. - Source: PubMed
Publication date: 2026/07/01
Lee SuboNéré RaphaelPark Kyoung SunJaquet VincentDemaurex NicolasPark Kyu-Sang - Dysfunctional adipocyte calcium handling is implicated in obesity and thermogenesis. Junctophilins (JPs) stabilize calcium microdomain junctions between the plasma membrane and endoplasmic reticulum, but whether JPs are required for adipocyte function is not known. We show that JP2 is enriched in thermogenic brown adipose tissue (BAT) relative to other fat depots and is downregulated under conditions of nutrient overload. Conditional knockdown of JP2 in adipocytes, and more selectively in BAT, exacerbates cold intolerance and susceptibility to diet induced obesity. Mechanistically, JP2-depleted brown adipocytes exhibit calcium handling dysfunction with elevated cytosolic calcium levels at baseline but diminished norepinephrine-induced calcium transients, reduced store-operated calcium entry. Basal cytosolic calcium overload accounts for an increase in calpain activation and ensuing downregulation of STIM1 and hormone-sensitive lipase in JP2-depleted cells. Furthermore, JP2 silencing in brown adipocytes reduced oxygen consumption rates and compromised mitochondrial structure and quality. Together, these findings demonstrate that JP2 is essential for normal calcium homeostasis in brown adipocytes and reveal a critical role for JP2 in thermogenesis and resistance to diet-induced metabolic dysregulation. - Source: PubMed
Publication date: 2026/06/29
Chen BiyiWang JinxiQian QingwenZhang GuangqinWang YihuiLi MarkTan RubinYang ZhuoyingZhao WeiyangCiampa GraceYang Bennett Daniela SarahiLiu YixiZhu QiZhu ZhiyongMasenga Sepiso KVue ZerLe HanShi QianZingman Leonid VHinton Antentor OHall Duane DAbel E DaleYang LingSong Long-Sheng