A5018232279- Ion Channels and Receptors
- Ion channel regulation and function
- Neurobiology and Insect Physiology Research
- Phytochemicals and Antioxidant Activities
- Lipid Membrane Structure and Behavior
- Calcium signaling and nucleotide metabolism
- Immune Cell Function and Interaction
- Toxin Mechanisms and Immunotoxins
- Biochemical Analysis and Sensing Techniques
- Cardiac electrophysiology and arrhythmias
- Inflammasome and immune disorders
- Magnesium in Health and Disease
- Biochemical effects in animals
- Connexins and lens biology
- Cellular transport and secretion
- Bioactive Compounds and Antitumor Agents
- Ancient and Medieval Archaeology Studies
- Adenosine and Purinergic Signaling
- Mitochondrial Function and Pathology
- Signaling Pathways in Disease
- Neuroscience and Neuropharmacology Research
- Heat shock proteins research
- Herbal Medicine Research Studies
- Redox biology and oxidative stress
- Plant Stress Responses and Tolerance
Saarland University
2015-2024
Staatliche Museen zu Berlin
2023
Berlin State Library
2023
Stanford University
2002
Hospital for Sick Children
2002
University of Cambridge
2002
Stanford Medicine
2000
Howard Hughes Medical Institute
1992-1996
University of California, San Diego
1995
The regulation of intracellular Ca2+ plays a key role in the development and growth cells. Here we report cloning functional expression highly calcium-selective channel localized on human chromosome 7. sequence new is structurally related to gene product CaT1 protein cloned from rat duodenum therefore called CaT-like (CaT-L). CaT-L expressed locally advanced prostate cancer, metastatic androgen-insensitive prostatic lesions but undetectable healthy tissue benign hyperplasia. Additionally,...
Reactive oxygen species (ROS) are involved in many physiological and pathophysiological cellular processes. We used lymphocytes, which exposed to highly oxidizing environments during inflammation, study the influence of ROS on function. Calcium ion (Ca(2+)) influx through Ca(2+) release-activated (CRAC) channels composed proteins ORAI family is essential for activation, proliferation, differentiation T but whether how affect channel function have been unclear. Here, we combined imaging,...
Abstract Cellular homeostasis relies upon precise regulation of Ca 2+ concentration. Stromal interaction molecule (STIM) proteins regulate store-operated calcium entry (SOCE) by sensing concentration in the ER and forming oligomers to trigger through plasma membrane-localized Orai1 channels. Here we characterize a STIM2 splice variant, STIM2.1 , which retains an additional exon within region encoding channel-activating domain. Expression is ubiquitous but its abundance relative more common...
Abstract Aims Inflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis animal models. Components NLRP3 pathway such as interleukin-1β can therapeutically be targeted. Associations genetically determined inflammasome-mediated systemic inflammation with CVD and mortality humans are unknown. Methods results We explored association genetic variants prevalent 538 167...
Background: Cardiovascular diseases and chronic kidney disease (CKD) are highly prevalent, aggravate each other, account for substantial mortality. Both conditions characterized by activation of the innate immune system. The alarmin interleukin-1α (IL-1α) is expressed in a variety cell types promoting (sterile) systemic inflammation. aim present study was to examine role IL-1α mediating inflammation setting acute myocardial infarction (AMI) CKD. Methods: We assessed expression on surface...
A finely tuned Ca(2+) signaling system is essential for cells to transduce extracellular stimuli, regulate growth, and differentiate. We have recently cloned CaT-like (CaT-L), a highly selective channel closely related the epithelial calcium channels (ECaC) transport protein CaT1. CaT-L expressed in selected exocrine tissues, its expression also strikingly correlates with malignancy of prostate cancer. The pattern permeation properties suggest an important function uptake role tumor...
Transient receptor potential (TRP) proteins form cation-conducting ion channels with currently 28 known genes encoding TRP channel monomers in mammals. These are thought to coassemble homo- or heterotetrameric channels, but the signals governing their assembly unknown. Within TRPV subgroup, TRPV5 and TRPV6 show exclusive calcium selectivity play an important role uptake. To identify that mediate of functional TRPV6, we screened domains for self-association using co-immunoprecipitation,...
T lymphocytes rely on a Ca 21 signal known as store-operated calcium entry (SOCE) for their activation.This is generated by activation of T-cell receptor, depletion endoplasmic reticulum (ER) stores and release-activated currents (I CRAC ).Here, we report that the ER protein orosomucoid like 3 (ORMDL3), product ORMDL3 gene associated with several autoimmune and/or inflammatory diseases, negatively modulates I , SOCE, nuclear factor activated cells translocation interleukin-2...
Summary Spontaneous melanoma phenotype switching is controlled by unknown environmental factors and may determine outcome responsiveness to anticancer therapy. We show that O rai1 STIM 2 are highly expressed control store‐operated C a 2+ entry in human melanoma. Lower extracellular or silencing of rai1/ caused decrease intracellular , which correlated with enhanced proliferation increased expression microphthalmia‐associated transcription factor, marker for proliferative phenotype. In...
Cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells are required to eliminate cancer cells. We analysed the Ca2+ dependence of CTL NK cell cytotoxicity found that in particular CTLs have a very low optimum [Ca2+ ]i (between 122 334 nm) ]o 23 625 μm) for efficient elimination, well below blood plasma levels. As predicted from these results, partial down-regulation channel Orai1 paradoxically increases perforin-dependent killing. Lytic granule release at immune synapse between has...
Reactive oxygen species (ROS) are emerging as important regulators of cancer growth and metastatic spread. However, how cells integrate redox signals to affect progression is not fully understood. Mitochondria cellular hubs, which highly regulated by interactions with neighboring organelles. Here, we investigated ROS at the endoplasmic reticulum (ER)-mitochondria interface generated translated melanoma outcome. We show that TMX1 TMX3 oxidoreductases, promote ER-mitochondria communication,...
Significance The work presents a unique understanding of the organization and function two ubiquitously expressed proteins, central in generating calcium signals all cell types. These are intracellular sensing “STIM” highly selective surface “Orai” channels. We reveal that STIM proteins can cross-link Orai channels, resulting reorganized microenvironment within membrane junctions which they function, with important consequences generation oscillatory signals. Interestingly, we show variant...
Store-operated Ca2+-entry (SOCE) regulates basal and receptor-triggered Ca2+ signaling with STIM proteins sensing the endoplasmic reticulum (ER) content triggering entry by gating Orai channels. Although crucial for immune cells, STIM1's role in neuronal homeostasis is controversial. Here, we characterize a splice variant, STIM1B, which shows exclusive expression protein surpassing conventional STIM1 cerebellum of significant abundance other brain regions. STIM1B results truncated slower...
TRPM (transient receptor potential melastatin-like) channels are distinct from many other members of the transient family in regard to their overall size (>1000 amino acids), lack N-terminal ankyrin-like repeats, and hydrophobicity predictions that may allow for more than six transmembrane regions. Common each member is a prominent C-terminal coiled coil region. Here we have shown TRPM8 assemble as multimers using putative region within intracellular C terminus this assembly can be disturbed...