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
- Calcium (Ca2+) signaling is a fundamental regulator of virtually all aspects of eukaryotic cell physiology, including gene expression, secretion, metabolism, motility, and cell fate decisions. The spatial and temporal control of cytosolic Ca2+ signals relies on a coordinated interplay between intracellular Ca2+ stores and plasma membrane (PM) Ca2+ channels. A critical advance in this field over the past two decades was the molecular identification of stromal interaction molecule 1 (STIM1) as the long-sought Ca2+ sensor that couples depletion of endoplasmic reticulum Ca2+ stores to Ca2+ influx across the PM. STIM1 has been established as a core component of store-operated Ca2+ entry, acting through direct activation of ORAI Ca2+ channels. However, accumulating evidence now indicates that STIM1 functions extend beyond this canonical role. STIM1 participates in the regulation of multiple classes of ion channels, contributes to the organization of membrane contact sites, and acts as a signaling scaffold influencing cellular processes independently of classical store depletion. This review summarizes the discovery and canonical functions of STIM1 and focuses on its emerging non-canonical roles, highlighting how STIM1 has evolved from an ER Ca2+ sensor into a multifunctional signaling hub. - Source: PubMed
Sanchez-Lopez IreneOrantos-Aguilera YolandaLopez-Guerrero Aida MPozo-Guisado EulaliaMartin-Romero Francisco Javier - Intracellular calcium (Ca) signaling controls myoblast proliferation, fusion, and myofiber formation. In myoblasts, Transient Receptor Potential Canonical (TRPC) channels, with TRPC1 as a predominant isoform, mediate store-operated Ca²⁺ entry (SOCE) and are essential for myogenesis. PDLIM5 (ENH1), a PDZ-LIM scaffold protein, organizes signaling events, including ion channel regulation and transcriptional control in muscles. This study aims to test the hypothesis that PDLIM5 regulates TRPC1-mediated Ca entry in myoblasts. Thapsigargin-induced SOCE was suppressed by the SOCE inhibitors Gd and 2-APB, as well as by TRPC1 siRNA, supporting the involvement of TRPC1 in SOCE in C2C12 myoblasts. Additionally, SOCE inhibition decreased the number of nuclei per myotube and reduced the size of myotubes. ENH1 siRNA knockdown significantly downregulated TRPC1 and STIM1 mRNA expression, increased basal cytosolic Ca level, and impaired SOCE response and myotube maturation. Overexpression of ENH4, a skeletal muscle-specific short splice variant of ENH1, similarly repressed TRPC1-mediated SOCE and myotube formation. Conversely, ENH1 overexpression enhanced SOCE without altering the mRNA levels of TRPC1, Orai1, or STIM1. Immunoprecipitation showed a physical interaction between ENH1/ENH4 and TRPC1. In differentiated myotubes, TRPC1 also contributed to thapsigargin-induced SOCE, as evidenced by the reduced Ca entry following TRPC1 knockdown. ENH1 knockdown and ENH4 overexpression significantly attenuated SOCE in myotubes; notably, ENH1 knockdown also increased basal cytosolic Ca level. In contrast to myoblasts, ENH1 overexpression did not enhance SOCE in myotubes, concomitant with the absence of a detectable interaction between ENH1 and TRPC1, whereas ENH4 retained its association with TRPC1. These findings suggest that ENH1 and ENH4 differentially modulate TRPC1-dependent Ca entry in C2C12 cells, thereby regulating myogenic differentiation and contributing to skeletal muscle formation and development. - Source: PubMed
Dong MingyiNiimi TomoakiMaturana Andrés Daniel - This study aimed to identify novel therapeutic targets for Alzheimer's disease (AD) by investigating the role of the intestinal flora (IF) via the gut-brain axis, and to predict a potential natural compound for AD treatment and elucidate its underlying mechanism. - Source: PubMed
Publication date: 2026/04/27
Ding TunanChen JunleiXiang YunshengZhou XiaojieZheng HongboBai YihanWang WeihaoFu QiangChen YanFu Yin - Advances in biomedicine have increased life expectancy, leading to a growing prevalence of age-related neurodegenerative diseases such as Alzheimer's and Parkinson's disease, alongside disorders of genetic or environmental origin including multiple sclerosis, Huntington's disease, and amyotrophic lateral sclerosis. Despite their diverse etiologies, these conditions share convergent pathogenic mechanisms-calcium overload, neuroinflammation, and oxidative stress-that drive neuronal apoptosis and progressive neurodegeneration. Developing therapies that effectively target these interconnected pathways remains a major challenge. Here, we applied a drug-repurposing pipeline integrating computational chemistry, calcium channel affinity prediction, and in vitro validation in SH-SY5Y and HEK293 cells. Eight clinically approved CNS drugs were screened for activity against Caᵥ1, Orai1, and P2X7 channels, and subsequently evaluated in neuroprotection assays. Several compounds demonstrated significant efficacy, with chlorpromazine showing broad-spectrum activity (neuroprotection, Caᵥ1.2 and P2X7 antagonism, anti-inflammatory effects), trimipramine emerging as a potent antioxidant, and vilazodone displaying synergistic neuroprotection in combination with procyclidine. These findings reveal multi-target pharmacological profiles in well-tolerated drugs not currently used for neurodegenerative indications. By highlighting both individual and combinatorial strategies, this work provides a foundation for translational studies aimed at repurposing approved agents for complex neurological disorders, with particular relevance to Parkinson's disease. - Source: PubMed
Publication date: 2026/04/28
Arasmou-Idrovo M SMarín-Rodríguez BGironda-Martínez AGarcía A GLeón RPascual-Guerra JTorres-Rico M - The immunological synapse (IS) is a nanoscale platform that coordinates T cell activation, cytoskeletal polarization, Ca signaling, and the directed secretion of lytic granules. In cancers, an acidic tumor microenvironment (TME; extracellular pH ~ 6.4-6.8) imposes a biophysical and metabolic stress that could destabilize this interface. Experimental studies indicate that even modest acidification could significantly reduce integrin-dependent adhesion strength, delay actin clearance at the synapse, and suppress store-operated Ca entry, thereby leading to marked decreases in cytokine production and cytotoxic granule release. In parallel, tumor cells often maintain relative intracellular alkalinity by enhancing proton export via transporters such as NHE1, MCT1/4, and CAIX, thereby reinforcing cortical actin "shielding," metabolic resilience, and resistance to perforin-mediated killing. These asymmetric pH adaptations may therefore establish a hidden checkpoint at the IS that favors tumor survival. We synthesize current evidence on pH-dependent regulation of actin dynamics, integrin activation, mitochondrial function, and Ca channels (Orai1/STIM1); highlight key methodological gaps, including the lack of approaches combining real-time intra- and extracellular pH and Ca imaging; and discuss enabling technologies such as microfluidic platforms, genetically encoded pH sensors, and multiparametric single-cell assays. Finally, we outline therapeutic strategies aimed at modulating pH (buffers, inhibitors of NHE1, MCTs, V-ATPases, or CAIX) or engineering pH-resistant effector cells and consider how these approaches could synergize with immune checkpoint blockade, CAR-T cells, and bispecific antibodies. Viewing acidosis as a druggable checkpoint reframes the IS as a bidirectional, pH-tuned system and suggests testable paths to restore antitumor immunity. - Source: PubMed
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