A5028219121- Ion Channels and Receptors
- Phytochemicals and Antioxidant Activities
- Neurobiology and Insect Physiology Research
- Ion channel regulation and function
- Respiratory and Cough-Related Research
- Postharvest Quality and Shelf Life Management
- Biochemical Analysis and Sensing Techniques
- Herbal Medicine Research Studies
- Cardiac electrophysiology and arrhythmias
- Insect Pest Control Strategies
- Toxin Mechanisms and Immunotoxins
- Neuropeptides and Animal Physiology
- Calcium signaling and nucleotide metabolism
- Effects and risks of endocrine disrupting chemicals
- Healthcare and Venom Research
- Microfluidic and Capillary Electrophoresis Applications
- Supramolecular Self-Assembly in Materials
- Insect and Pesticide Research
- Advanced Fluorescence Microscopy Techniques
- Microbial Inactivation Methods
- Force Microscopy Techniques and Applications
- Polymer crystallization and properties
- Neuroscience and Neuropharmacology Research
- Plant Stress Responses and Tolerance
- Botanical Research and Chemistry
Johannes Kepler University of Linz
2011-2021
Czech Academy of Sciences, Institute of Biophysics
2013
Albany Medical Center Hospital
2013
University at Albany, State University of New York
2013
Albany State University
2013
Eastern Virginia Medical School
2013
Tulane University
2013
Institute of Biophysics
2008-2009
STIM1 and ORAI1 (also termed CRACM1) are essential components of the classical calcium release-activated current; however, mechanism transmission information to calcium/ORAI1 channel is as yet unknown. Here we demonstrate by Förster resonance energy transfer microscopy a dynamic coupling that culminates in activation Ca2+ entry. imaging living cells provided insight into time dependence crucial events this signaling pathway comprising store depletion, multimerization, STIM1-ORAI1...
In immune cells, generation of sustained Ca(2+) levels is mediated by the release-activated (CRAC) current. Molecular key players in this process comprise stromal interaction molecule 1 (STIM1) that functions as a sensor endoplasmic reticulum and ORAI1 located plasma membrane. Depletion stores leads to STIM1 multimerization into discrete puncta, which co-cluster with couple activate channels. The cytosolic C terminus sufficient currents independent store depletion. Here we identified an...
Orai1 calcium channels in the plasma membrane are activated by stromal interaction molecule-1 (STIM1), an endoplasmic reticulum sensor, to mediate store-operated entry (SOCE). The cytosolic region of STIM1 contains a long putative coiled-coil (CC)1 segment and shorter CC2 CC3 domains. Here we present solution nuclear magnetic resonance structures trypsin-resistant CC1–CC2 fragment apo Orai1-bound states. Each subunit forms U-shaped structure that homodimerizes through antiparallel...
STIM1 and Orai1 have been reported to interact upon store depletion culminating in Ca(2+) release-activated current activation. Recently, the essential region has identified within C terminus that includes second coiled-coil domain C-terminally extended by approximately 50 amino acids exhibits a strong binding terminus. Based on homology Orai family, an analogous scenario might be assumed for Orai2 as well Orai3 channels both are activated similar STIM1-dependent manner. A combined approach...
Through largely unknown mechanisms, Ca(2+) signaling plays important roles in vascular smooth muscle cell (VSMC) remodeling. Orai1-encoded store-operated entry has recently emerged as an player VSMC However, the role of exclusively mammalian Orai3 protein native pathways, its upregulation during remodeling, and contribution to neointima formation remain unknown.The goal this study was determine agonist-evoked pathway contributed by Orai3; potential after balloon injury rat carotid...
Stim1 in the endoplasmic reticulum and three Orai (also termed CRACM) channels plasma-membrane are main components of native Ca2+ release-activated channels. A pharmacological hallmark these is their distinct sensitivity to 2-aminoethoxydiphenyl borate (2-APB). Here we report that Orai3 currents can be robustly stimulated by 75 μm 2-APB independent Stim1, whereas at similar concentrations inhibited store-operated Orai1 currents. did not only promote through but also dramatically altered ion...
STIM1 and ORAI1, the two limiting components in Ca(2+) release-activated (CRAC) signaling cascade, have been reported to interact upon store depletion, culminating CRAC current activation. We recently identified a modulatory domain between amino acids 474 485 cytosolic part of that comprises 7 negatively charged residues. A C-terminal fragment lacking this exhibits enhanced interaction with ORAI1 2-3-fold higher ORAI1/CRAC densities. Here we focused on role (CMD) fast inactivation channels,...
The Ca(2+)-selective TRPV6 as well the L-type Ca(2+) channel are regulated by Ca(2+)-binding protein calmodulin (CaM). Here, we investigated interaction of CaM with rat (r)TRPV6 in response to alterations intracellular Ca(2+), employing Ca(2+)-imaging and patch-clamp techniques. Additionally, confocal Förster resonance energy transfer (FRET) microscopy on living cells was utilized a key method visualize vivo protein-protein interactions essential for regulation rTRPV6 activity. effects...
Cholesterol suppresses the activity of a channel needed to refill intracellular calcium stores.
Characterization of disease-associated Orai1 mutants reveals the multistep gating mechanism for CRAC channel.
Store-operated Ca(2+) entry (SOCE) is a universal influx pathway that important for the function of many cell types. SOCE occurs upon depletion endoplasmic reticulum (ER) stores and relies on complex molecular interplay between plasma membrane (PM) channel ORAI1 ER sensor stromal interaction molecule (STIM) 1. Patients with null mutations in or STIM1 genes present severe combined immunodeficiency (SCID)-like disease. Here, we describe mechanisms by which loss-of-function mutation (R429C)...
The Ca(2+) release-activated channel mediates influx in a plethora of cell types, thereby controlling diverse cellular functions. complex is composed stromal interaction molecule 1 (STIM1), an endoplasmic reticulum Ca(2+)-sensing protein, and Orai1, plasma membrane channel. Channels STIM1 Orai1 mediate even at low extracellular concentrations. We investigated whether the activity adapted to different environmental used homology modeling molecular dynamics simulations predict presence...
STIM1 and Orai1 are key components of the Ca2+-release activated Ca2+ (CRAC) current. Orai1, which represents subunit forming CRAC channel complex, is by ER resident sensor STIM1. The genetically inherited Stormorken syndrome disease has been associated with single point R304W mutant. resulting constitutive activation mainly involves CRAC-activating domain CAD/SOAR STIM1, exposure regulated molecular interplay between three cytosolic coiled-coil (CC) domains. Here we present a dual mechanism...
Calcium signalling through store-operated calcium (SOC) entry is of crucial importance for T-cell activation and the adaptive immune response. This occurs via prototypic Ca2+ release-activated (CRAC) channel. STIM1, a key molecular component this process, located in membrane endoplasmic reticulum (ER) initially activated upon store depletion. signal transmitted to plasma direct physical interaction that takes place between STIM1 highly Ca2+-selective ion channel Orai1. The induces an...
A general cellular response following depletion of intracellular calcium stores involves activation store-operated channels (SOCs). While Orai1 forms the native Ca(2+) release-activated (CRAC) channel in mast and T cells, molecular architecture less selective SOCs is insufficiently defined. Here we present evidence that diminished selectivity robust Cs(+) permeation together with a reduced fast inactivation are characteristics heteromeric Orai3 contrast to their homomeric forms. The first...
Activation of immune cells is triggered by the Ca2+ release-activated current, which mediated via channels Orai protein family. A key gating process three channel isoforms to prevent overload fast inactivation, most pronounced in Orai3. subsequent reactivation a unique characteristic Orai1 channels, whereas Orai2 and Orai3 currents display second, slow inactivation phase. Employing chimeric approach sequential swapping respective intra- extracellular regions between Orai3, we show here that...
We recently showed, in primary vascular smooth muscle cells (VSMCs), that the platelet-derived growth factor activates canonical store-operated Ca2+ entry and release-activated currents encoded by Orai1 STIM1 genes. However, thrombin store-independent selective channels contributed both Orai3 Orai1. These Orai3/Orai1 are gated cytosolic leukotriene C4 (LTC4) require downstream LTC4 action. source of signaling mechanisms activation this LTC4-regulated (LRC) channel unknown. Here, we show upon...