Ask about this productRelated genes to: ORAI1 Blocking Peptide
- 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 Blocking Peptide
Related articles to: ORAI1 Blocking Peptide
- Crosslinking of the high affinity IgE receptor (FcεRI) by multivalent antigen increases intracellular Ca concentration ([Ca]) through two sequential steps: (i) Ca release from the endoplasmic reticulum (ER) and (ii) store-operated Ca entry (SOCE) mediated by stromal interaction molecule 1 (STIM1)-Orai1 interaction. This process is essential for basophil and mast cell activation. We previously showed that FcεRI disaggregation by monomeric hapten rapidly and persistently inhibited [Ca] increase although upstream signal disruption was transient in rat basophilic leukemia cells. However, the underlying inhibitory mechanisms remain unclear. In this study, we found that monomeric hapten dissociates STIM1-Orai1 interaction by promoting Orai1 re-phosphorylation. Although Ca release from ER, the first step in [Ca] increase, was blocked by monomeric hapten addition, phosphorylation of phospholipase Cγ1, a critical step for Ca release from the ER, was inhibited only when the monomeric hapten was added immediately after multivalent antigen stimulation, but not when added several minutes later. However, STIM1-Orai1 interaction was dissociated by the monomeric hapten, regardless of the timing of its addition. Multivalent antigen induced Orai1 dephosphorylation, which is necessary for SOCE. In contrast, monomeric hapten addition promoted its re-phosphorylation. These results suggest that cessation of [Ca] increase following FcεRI disaggregation primarily arises from immediate suppression of SOCE via STIM1-Orai1 dissociation. - Source: PubMed
Publication date: 2026/09/04
Suzuki RurikoOgawa RinkaFuruno Tadahide - Neurovascular coupling ensures that active neuronal circuits receive the blood supply needed to sustain brain function. In this issue of , Lavanderos identify STIM1-ORAI-mediated Ca entry as a mechanism that reinforces capillary-to-arteriole communication, sustaining functional hyperemia during repetitive neuronal stimulation. - Source: PubMed
Publication date: 2026/09/01
Dabertrand Fabrice - Neurovascular coupling (NVC), which is initiated by the brain's dense capillary network, matches blood flow to neuronal activity. We found that ORAI1 channels and their regulator STIM1, the main drivers of store-operated Ca entry, were essential for communication from capillaries, which detect neuronal metabolic need, to upstream arterioles, which dilate to increase regional flow. Endothelial cell-specific knockout of either or disrupted capillary Ca signals, impaired sustained capillary-driven arteriole dilation, and reduced increases in blood flow in the somatosensory cortex evoked by whisker stimulation, indicating that ORAI1 and STIM1 sustain cerebral blood flow during prolonged neuronal stimulation. Moreover, mice with endothelial cell-specific deficiency of or showed cognitive impairment, whereas mice with endothelial cell-specific deficiency of showed anxiety-like behaviors. These in vivo results link impaired capillary-to-arteriole signaling to isoform-specific behavioral aberrations. These findings demonstrate that intravascular communication mediated by ORAI channels and STIM1 is fundamental for NVC and brain health. - Source: PubMed
Publication date: 2026/09/01
Lavanderos BorisSanchez-Solano AlfredoZhu WanchunThakore PratishYamasaki EvanChen YilinFeng Earley YumeiTrebak MohamedEarley Scott - Orai1, the pore-forming subunit of the calcium (Ca2+) release-activated Ca2+ (CRAC) channel, plays a central role in store-operated Ca2+ entry (SOCE) in animal cells and thereby serves as a key regulator of intracellular Ca2+ homeostasis. Disruption of this tightly controlled process is associated with a wide spectrum of human diseases. Dysfunction can result from a multitude of remodeling mechanisms, including altered protein expression (up- or downregulation), assembly remodeling, or mutations. We focus in particular on Orai1 mutations, which have been linked to severe combined immunodeficiency (SCID) as a result of channel loss-of-function (LoF), as well as to disorders like tubular aggregate myopathy (TAM) and Stormorken syndrome (STRMK) arising from gain-of-function (GoF) alterations. These mutation-induced functional defects can be attributed to a wide variety of disruptions in the complex activation cascade of the Orai1 channel. Under physiological conditions, Orai1 activation involves all four transmembrane (TM) domains and follows a sophisticated interaction mechanism that ensures accurate signal transmission from the protein periphery toward its central Ca2+-conducting pore. In this Review, we compile all currently known disease-associated Orai1 mutations, delineate the mechanisms by which they interfere with the activation cascade, and discuss their pathological relevance. Their widespread distribution across all the domains of this Ca2+ channel highlights that malfunctions at virtually any point along the Orai1 TM domain interfaces can profoundly impair its activation mechanism, ultimately leading to severe diseases. - Source: PubMed
Publication date: 2026/08/31
Prantl MagdalenaAtzgerstorfer LaraRadiskovic TamaraFahrner MarcDerler Isabella - Platelet-activating factor (PAF) is known to induce smooth muscle contraction; however, its mechanisms in urinary bladder smooth muscle (UBSM) remain unclear. We investigated the involvement of Orai1 in PAF-induced contraction in guinea pig UBSM. PAF (10 M)-induced contraction was markedly inhibited by the Orai1 inhibitor Synta66 (10 M) and the L-type voltage-dependent Ca channel (VDCC) inhibitor verapamil (10 M). Similarly, under Ca-free conditions with store depletion induced by cyclopiazonic acid (3 × 10 M), Ca-induced contraction was suppressed by Synta66 and verapamil. In contrast, Synta66 only partially inhibited contractions induced by acetylcholine (10 M) and α,β-methylene ATP (3 × 10 M), and it had no effect on high-potassium chloride (80 mM)-induced contraction. Inhibition of Na/Ca exchanger 1 (NCX1), transient receptor potential canonical (TRPC) 1/4/5 channels, or anoctamin 1 (ANO1) did not significantly affect PAF-induced contraction. These findings suggest that Orai1 contributes to PAF-induced contraction in association with VDCC-dependent mechanisms, whereas NCX1, TRPC1/4/5 channels, and ANO1 play limited roles under these conditions. - Source: PubMed
Obara KeisukeKato DaikiYuguchi MarinaTanaka MomokoYoshioka KentoNakamichi NoritakaTanaka Yoshio