Feedback modulation of Orai1α and Orai1β protein content mediated by STIM proteins.

Store-operated Ca entry is a mechanism controlled by the filling state of the intracellular Ca stores, predominantly the endoplasmic reticulum (ER), where ER-resident proteins STIM1 and STIM2 orchestrate the activation of Orai channels in the plasma membrane, and Orai1 playing a predominant role. Two forms of Orai1, Orai1α and Orai1β, have been identified, which arises the question whether they are equally regulated by STIM proteins. We demonstrate that STIM1 preferentially activates Orai1α over STIM2, yet both STIM proteins similarly activate Orai1β.

Differential functional role of Orai1 variants in constitutive Ca entry and calcification in luminal breast cancer cells.

Resting cytosolic Ca concentration is tightly regulated to fine-tune Ca-dependent cellular functions. Luminal breast cancer cells exhibit constitutive Ca entry mediated by Orai1 and the secretory pathway Ca-ATPase, SPCA2, which result in mammary microcalcifications that constitute a prognostic marker of mammary lesions. Two Orai1 isoforms have been identified, the full-length Orai1α, consisting of 301 amino acids, and the short variant, Orai1β, lacking the 63 or 70 N-terminal amino acids comprising residues involved in channel inactivation and binding sites with Orai1 partners.

Extended Synaptotagmins 1 and 2 Are Required for Store-Operated Calcium Entry, Cell Migration and Viability in Breast Cancer Cells.

Extended synaptotagmins (E-Syts) are endoplasmic reticulum (ER)-associated proteins that facilitate the tethering of the ER to the plasma membrane (PM), participating in lipid transfer between the membranes and supporting the Orai1-STIM1 interaction at ER-PM junctions. Orai1 and STIM1 are the core proteins of store-operated Ca entry (SOCE), a major mechanism for Ca influx that regulates a variety of cellular functions. Aberrant modulation of SOCE in cells from different types of cancer has been reported to underlie the development of several tumoral features.

Combining Sound and Deep Neural Networks for the Measurement of Jump Height in Sports Science.

Jump height tests are employed to measure lower-limb muscle power of athletic and non-athletic populations. The most popular instruments for this purpose are jump mats and, in recent years, smartphone apps, which compute jump height through the manual annotation of video recordings and recently automatically using the sound produced during the jump to extract the flight time. In a previous work, the afore-mentioned sound systems were presented by the authors in which the take-off and landing events from the audio recordings of jump executions were obtained using classical signal processing.

Postbiotics of Lacticaseibacillus paracasei CECT 9610 and Lactiplantibacillus plantarum CECT 9608 attenuates store-operated calcium entry and FAK phosphorylation in colorectal cancer cells.

Store-operated Ca entry (SOCE) is a major mechanism for Ca influx in colorectal cancer (CRC) cells. This mechanism, regulated by the filling state of the intracellular Ca stores, is mediated by the endoplasmic reticulum Ca sensors of the stromal interaction molecules (STIM) family [stromal interaction molecule 1 (STIM1) and STIM2] and the Ca-release-activated Ca channels constituted by Orai family members, with predominance of calcium release-activated calcium channel protein 1 (Orai1). CRC cells exhibit enhanced SOCE due to remodeling of the expression of the key SOCE molecular components.

Orai1α and Orai1β support calcium entry and mammosphere formation in breast cancer stem cells.

Orai1 is the pore-forming subunit of the Ca-release activated Ca channels that mediate store-operated Ca entry (SOCE) in excitable and non-excitable cells. Two Orai1 forms have been identified in mammalian cells, the full-length variant Orai1α, and the short form Orai1β, lacking the N-terminal 63 amino acids. Stem cells were isolated from non-tumoral breast epithelial cells of the MCF10A cell line, and the most representative ER+ , HER2 or triple negative breast cancer cell lines MCF7, SKBR3 and MDA-MB-231, respectively.

The Ca Sensor STIM in Human Diseases.

The STIM family of proteins plays a crucial role in a plethora of cellular functions through the regulation of store-operated Ca entry (SOCE) and, thus, intracellular calcium homeostasis. The two members of the mammalian STIM family, STIM1 and STIM2, are transmembrane proteins that act as Ca sensors in the endoplasmic reticulum (ER) and, upon Ca store discharge, interact with and activate the Orai/CRACs in the plasma membrane. Dysregulation of Ca signaling leads to the pathogenesis of a variety of human diseases, including neurodegenerative disorders, cardiovascular diseases, cancer, and immune disorders.

Intravenous Administration of Umbilical Cord-Derived Mesenchymal Stem Cells (UC-MSC) for Acute Respiratory Distress Syndrome Due to COVID-19 Infection.

The COVID-19 pandemic has posed significant therapeutic challenges in addressing acute respiratory distress syndrome (ARDS). This serious illness has caused numerous fatalities worldwide and has had profound health and economic impacts. Previous studies have shown that mesenchymal stem cells (MSCs) can suppress ARDS.

Functional differences in agonist-induced plasma membrane expression of Orai1α and Orai1β.

Orai1 is the pore-forming subunit of the store-operated Ca release-activated Ca (CRAC) channels involved in a variety of cellular functions. Two Orai1 variants have been identified, the long form, Orai1α, containing 301 amino acids, and the short form, Orai1β, which arises from alternative translation initiation from methionines 64 or 71, in Orai1α. Orai1 is mostly expressed in the plasma membrane, but a subset of Orai1 is located in intracellular compartments.

Role of Orai-family channels in the activation and regulation of transcriptional activity.

Store operated Ca entry (SOCE) is a cornerstone for the maintenance of intracellular Ca homeostasis and the regulation of a variety of cellular functions. SOCE is mediated by STIM and Orai proteins following the activation of inositol 1,4,5-trisphosphate receptors. Then, a reduction of the endoplasmic reticulum intraluminal Ca concentration is sensed by STIM proteins, which undergo a conformational change and activate plasma membrane Ca channels comprised by Orai proteins.

Correction: Sanchez-Collado et al. Orai2 Modulates Store-Operated Ca Entry and Cell Cycle Progression in Breast Cancer Cells. 2021, , 114.

In the original publication [...

The store-operated Ca channel Orai1α is required for agonist-evoked NF-κB activation by a mechanism dependent on PKCβ2.

Store-operated Ca entry is a ubiquitous mechanism for Ca influx in mammalian cells that regulates a variety of physiological processes. The identification of two forms of Orai1, the predominant store-operated channel, Orai1α and Orai1β, raises the question whether they differentially regulate cell function. Orai1α is the full-length Orai1, containing 301 amino acids, whereas Orai1β lacks the N-terminal 63 amino acids.

Store-Operated Calcium Entry in Breast Cancer Cells Is Insensitive to Orai1 and STIM1 N-Linked Glycosylation.

N-linked glycosylation is a post-translational modification that affects protein function, structure, and interaction with other proteins. The store-operated Ca entry (SOCE) core proteins, Orai1 and STIM1, exhibit N-glycosylation consensus motifs. Abnormal SOCE has been associated to a number of disorders, including cancer, and alterations in Orai1 glycosylation have been related to cancer invasiveness and metastasis.

Similarities and Differences between the Orai1 Variants: Orai1α and Orai1β.

Orai1, the first identified member of the Orai protein family, is ubiquitously expressed in the animal kingdom. Orai1 was initially characterized as the channel responsible for the store-operated calcium entry (SOCE), a major mechanism that allows cytosolic calcium concentration increments upon receptor-mediated IP generation, which results in intracellular Ca store depletion. Furthermore, current evidence supports that abnormal Orai1 expression or function underlies several disorders.

Store-Operated Calcium Entry and Its Implications in Cancer Stem Cells.

Tumors are composed by a heterogeneous population of cells. Among them, a sub-population of cells, termed cancer stem cells, exhibit stemness features, such as self-renewal capabilities, disposition to differentiate to a more proliferative state, and chemotherapy resistance, processes that are all mediated by Ca. Ca homeostasis is vital for several physiological processes, and alterations in the patterns of expressions of the proteins and molecules that modulate it have recently become a cancer hallmark.

Orai2 Modulates Store-Operated Ca Entry and Cell Cycle Progression in Breast Cancer Cells.

Breast cancer is a heterogeneous disease from the histological and molecular expression point of view, and this heterogeneity determines cancer aggressiveness. Store-operated Ca entry (SOCE), a major mechanism for Ca entry in non-excitable cells, is significantly remodeled in cancer cells and plays an important role in the development and support of different cancer hallmarks. The store-operated CRAC (Ca release-activated Ca) channels are predominantly comprised of Orai1 but the participation of Orai2 and Orai3 subunits has been reported to modulate the magnitude of Ca responses.

Orai1α, but not Orai1β, co-localizes with TRPC1 and is required for its plasma membrane location and activation in HeLa cells.

The identification of two variants of the canonical pore-forming subunit of the Ca release-activated Ca (CRAC) channel Orai1, Orai1α and Orai1β, in mammalian cells arises the question whether they exhibit different functional characteristics. Orai1α and Orai1β differ in the N-terminal 63 amino acids, exclusive of Orai1α, and show different sensitivities to Ca-dependent inactivation, as well as distinct ability to form arachidonate-regulated channels. We have evaluated the role of both Orai1 variants in the activation of TRPC1 in HeLa cells.

A Fibrin Coating Method of Polypropylene Meshes Enables the Adhesion of Menstrual Blood-Derived Mesenchymal Stromal Cells: A New Delivery Strategy for Stem Cell-Based Therapies.

Polypropylene (PP) mesh is well-known as a gold standard of all prosthetic materials of choice for the reinforcement of soft tissues in case of hernia, organ prolapse, and urinary incontinence. The adverse effects that follow surgical mesh implantation remain an unmet medical challenge. Herein, it is outlined a new approach to allow viability and adhesion of human menstrual blood-derived mesenchymal stromal cells (MenSCs) on PP surgical meshes.

Characterization of the import applications for unavailable vital medicines in 2016 and 2017 in Colombia.

This study analyzed the import applications for unavailable vital medicines (MVND) submitted to INVIMA and the records of MVND reimbursement requests submitted to the ADRES in the 2016-2017 period. Approximately 76% of the 2,321 MVND import applications were authorized. Eighty-eight applicants, 73 therapeutic subgroups, 195 active ingredients, and 368 diagnoses were identified.

Role of Orai3 in the Pathophysiology of Cancer.

The mammalian exclusive Orai3 channel participates in the generation and/or modulation of two independent Ca currents, the store-operated current, I, involving functional interactions between the stromal interaction molecules (STIM), STIM1/STIM2, and Orai1/Orai2/Orai3, as well as the store-independent arachidonic acid (AA) (or leukotriene C4)-regulated current I, which involves Orai1, Orai3 and STIM1. Overexpression of functional Orai3 has been described in different neoplastic cells and cancer tissue samples as compared to non-tumor cells or normal adjacent tissue. In these cells, Orai3 exhibits a cell-specific relevance in Ca influx.

SARAF and EFHB Modulate Store-Operated Ca Entry and Are Required for Cell Proliferation, Migration and Viability in Breast Cancer Cells.

Breast cancer is among the most common malignancies in women. From the molecular point of view, breast cancer can be grouped into different categories, including the luminal (estrogen receptor positive (ER+)) and triple negative subtypes, which show distinctive features and, thus, are sensitive to different therapies. Breast cancer cells are strongly dependent on Ca influx.

The Orai1-AC8 Interplay: How Breast Cancer Cells Escape from Orai1 Channel Inactivation.

The interplay between the Ca-sensitive adenylyl cyclase 8 (AC8) and Orai1 channels plays an important role both in the activation of the cAMP/PKA signaling and the modulation of Orai1-dependent Ca signals. AC8 interacts with a N-terminal region that is exclusive to the Orai1 long variant, Orai1α. The interaction between both proteins allows the Ca that enters the cell through Orai1α to activate the generation of cAMP by AC8.

Furin Prodomain ppFurin Enhances Ca Entry Through Orai and TRPC6 Channels' Activation in Breast Cancer Cells.

The intracellular calcium concentration ([Ca]) modulation plays a key role in the regulation of cellular growth and survival in normal cells and failure of [Ca] homeostasis is involved in tumor initiation and progression. Here we showed that inhibition of Furin by its naturally occurring inhibitor the prodomain ppFurin in the MDA-MB-231 breast cancer cells resulted in enhanced store-operated calcium entry (SOCE) and reduced the cell malignant phenotype. Expression of ppFurin in a stable manner in MDA-MB-231 and the melanoma MDA-MB-435 cell lines inhibits Furin activity as assessed by in vitro digestion assays.

Video-Based System for Automatic Measurement of Barbell Velocity in Back Squat.

Velocity-based training is a contemporary method used by sports coaches to prescribe the optimal loading based on the velocity of movement of a load lifted. The most employed and accurate instruments to monitor velocity are linear position transducers. Alternatively, smartphone apps compute mean velocity after each execution by manual on-screen digitizing, introducing human error.

Cross-Talk Between the Adenylyl Cyclase/cAMP Pathway and Ca Homeostasis.

Cyclic AMP and Ca are the first second or intracellular messengers identified, unveiling the cellular mechanisms activated by a plethora of extracellular signals, including hormones. Cyclic AMP generation is catalyzed by adenylyl cyclases (ACs), which convert ATP into cAMP and pyrophosphate. By the way, Ca, as energy, can neither be created nor be destroyed; Ca can only be transported, from one compartment to another, or chelated by a variety of Ca-binding molecules.