Ask about this productRelated genes to: ORAI1 antibody
- Gene:
- ORAI1 NIH gene
- Name:
- ORAI calcium release-activated calcium modulator 1
- Previous symbol:
- TMEM142A
- Synonyms:
- FLJ14466, CRACM1
- Chromosome:
- 12q24.31
- Locus Type:
- gene with protein product
- Date approved:
- 2006-04-10
- Date modifiied:
- 2019-04-23
Related products to: ORAI1 antibody
Related articles to: ORAI1 antibody
- 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 - Combined immunodeficiency (CID) due to deficiency is an ultrarare autosomal recessive disorder characterized by the coexistence of recurrent infections, ectodermal dysplasia, autoimmunity, and myopathy. Untreated patients die in early childhood due to recurrent severe infections. This report presents a familial case of CID due to ORAI1 deficiency, caused by a homozygous loss-of-function variant c.581T>C in the gene. The oldest of the siblings died because of recurrent severe infections in the third year of life. His brother survived because of hematopoietic cell transplantation (HCT) but developed other symptoms of the disease. The patient achieved the ability to walk unaided at age 18 months, with a waddling gait from the beginning. His neurologic status was stable in early childhood, with mild deterioration after age 6 years. At the age of 11 years, proximal muscle weakness and borderline respiratory sufficiency are observed, with myopathic electromyography, normal level of creatine kinase, and global fatty infiltration in muscle magnetic resonance imaging, most pronounced in gluteus maximus. Additionally, dental dysplasia and heat intolerance are observed. Keywords: ORAI1 deficiency, combined immunodeficiency, gene, neuromuscular symptoms, myopathy. - Source: PubMed
Publication date: 2026/07/02
Jędrzejowska MariaPotulska-Chromik AnnaCzeczko KarolinaFranaszczyk MariaWolska-Kuśnierz BeataRosiak EdytaAragon-Gawińska KarolinaStokłosa TomaszKostera-Pruszczyk Anna - 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 - Osteoporotic fracture healing is impaired by dysregulated immune responses characterized by a T1/M1-biased inflammatory microenvironment. In this study, we show that extracellular magnesium ions (Mg) reshape this osteo-immune niche in a dose- and time-dependent manner. Briefly, Mg suppresses TRPM7-mediated Ca spikes and the NFATc1-driven proinflammatory axis, thereby promoting T2/M2 responses. However, sustained excess Mg attenuates T2/M2 responses by inhibiting Orai1/CaV-dependent Ca influx and reactivating T1/M1 responses through JAK-STAT1 signaling under low-calcium stimulation condition. To therapeutically use these dynamics, we engineered a bioceramic intramedullary nail (IMN) with a precisely controlled Mg release profile, delivering Mg in a time-phased manner. In an ovariectomized mouse fracture model, this optimized IMN reduced T1/M1 of early phase proinflammatory cells, enhanced T2/M2 responses during the remodeling phase, and supported coordinated immune regulation during osteoporotic fracture healing. These findings identify time-phased Mg delivery as a strategy to mitigate excessive inflammatory responses through temporal immunomodulation of CD4 T cells during osteoporotic bone healing. - Source: PubMed
Publication date: 2026/06/26
Kim Jung HunKang Tae HoonJeon SuWanHwang Nathaniel S - PIGBOS is a recently identified 54-amino acid microprotein localized to the mitochondrial outer membrane and implicated in the endoplasmic reticulum (ER) stress response. Here, we identify a previously unrecognized role for PIGBOS in cellular Ca homeostasis. Manipulation of PIGBOS expression in HEK293T cells revealed that PIGBOS enhances Ca signaling by promoting ER Ca release through inositol 1,4,5-trisphosphate (IP) receptors and subsequent mitochondrial Ca uptake in response to histamine stimulation. In contrast, siRNA-mediated depletion or genetic ablation of PIGBOS markedly attenuated these responses. PIGBOS influenced Ca transfer from the ER to mitochondria without affecting direct mitochondrial Ca uptake and also promoted store-operated Ca entry. Functional analyses demonstrated that the interaction of PIGBOS with the ER-resident chloride channel CLCC1 via its C-terminal region is required for this activity. Network analysis predicted a direct association between PIGBOS and CLCC1, as well as indirect connections with core Ca signaling components, including IP receptors, STIM1, Orai1, and SERCA, whose expression was altered upon modulation of PIGBOS abundance. Loss of PIGBOS impaired mitochondrial respiration, reduced ATP production, and increased reactive oxygen species. Together, these findings establish PIGBOS as a key regulator of ER-mitochondrial Ca signaling that couples Ca dynamics to mitochondrial bioenergetics and cellular stress responses. - Source: PubMed
Publication date: 2026/06/25
Aditya SeemantiBera Amal Kanti