A5028242281- Calcium signaling and nucleotide metabolism
- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Ion Channels and Receptors
- Autophagy in Disease and Therapy
- Atrial Fibrillation Management and Outcomes
- Protein Kinase Regulation and GTPase Signaling
- Cardiac Arrhythmias and Treatments
- Neuroscience and Neuropharmacology Research
- Lysosomal Storage Disorders Research
- Adenosine and Purinergic Signaling
- Neurobiology and Insect Physiology Research
- Cardiovascular Disease and Adiposity
- Cardiovascular Function and Risk Factors
- Parathyroid Disorders and Treatments
- Pancreatic function and diabetes
- Insects and Parasite Interactions
- Sperm and Testicular Function
- Reproductive Biology and Fertility
- Insect and Arachnid Ecology and Behavior
- Cellular transport and secretion
- Trace Elements in Health
- Advanced Fluorescence Microscopy Techniques
- Protease and Inhibitor Mechanisms
- Receptor Mechanisms and Signaling
The Open University
2014-2025
University of Oxford
2009-2015
Milton Keynes Hospital
2015
University of Massachusetts Chan Medical School
2013-2014
Babraham Institute
2003-2012
Cornell University
2010
University of Córdoba
2010
Toxicologie, Pharmacologie et Signalisation Cellulaire
2008
University of Potsdam
2002-2005
Imbalance of signals that control cell survival and death results in pathologies, including cancer neurodegeneration. Two pathways are integral to setting the balance between controlled by lipid-activated protein kinase B (PKB)/Akt Ca(2+). PKB elicits its effects through phosphorylation inactivation proapoptotic factors. Ca(2+) stimulates many prodeath pathways, among which is mitochondrial permeability transition. We identified release inositol 1,4,5-trisphosphate receptor (InsP(3)R)...
SummaryIntracellular Ca2+ signals constitute key elements in signal transduction. Of the three major mobilizing messengers described, most potent, nicotinic acid adenine dinucleotide phosphate (NAADP) is least well understood terms of its molecular targets [1]. Recently, we showed that heterologous expression two-pore channel (TPC) proteins enhances NAADP-induced release, whereas NAADP response was abolished pancreatic beta cells from Tpcn2 gene knockout mice [2]. However, whether TPCs...
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a molecule capable of initiating the release intracellular Ca<sup>2+</sup> required for many essential cellular processes. Recent evidence links two-pore channels (TPCs) with NAADP-induced from lysosome-like acidic organelles; however, there has been no direct demonstration that TPCs can act as NAADP-sensitive channels. Controversial also proposes ryanodine receptors primary target NAADP. We show TPC2, major lysosomal targeted isoform,...
Calcilytics reduce airway hyperresponsiveness and inflammation may represent effective asthma therapeutics.
Imaging Ca 2+ -sensitive fluorescent indicators provides a common approach for studying signals in many contexts. Fluorescent are particularly useful measuring acute changes relatively noninvasive manner. The availability of that can be targeted to specific cellular domains, coupled with variations affinity, brightness or spectral characteristics, tools exploring spatially and temporally diverse signals, moreover, multiplexing the readout other functions. This article aims give novice...
Article18 December 2003free access Regulation of InsP3 receptor activity by neuronal Ca2+-binding proteins Nael Nadif Kasri Laboratorium voor Fysiologie, KU Leuven, Campus Gasthuisberg O/N, Belgium Search for more papers this author Anthony M Holmes Babraham Institute, Cambridge, UK Geert Bultynck Jan B Parys Martin D Bootman Katja Rietdorf Ludwig Missiaen Fraser McDonald Department Orthodontics, GKT Dental Kings College London, Humbert De Smedt Stuart J Conway Chemistry, University Andrew...
Recent studies into the mechanisms of action Ca2+-mobilizing messenger NAADP (nicotinic acid–adenine dinucleotide phosphate) have demonstrated that a novel family intracellular Ca2+-release channels termed TPCs (two-pore channels) are components receptor. appear to be exclusively localized endolysosomal system. These findings confirm previous pharmacological and biochemical suggesting targets acidic Ca2+ stores rather than endoplasmic reticulum, major site other two principal messengers,...
Mammalian oocyte activation occurs via a series of intracellular calcium (Ca2+) oscillations thought to be induced by sperm-specific phospholipase C zeta (PLCζ). There is now strong evidence indicate that certain types human male infertility are caused failure the sperm activate in an appropriate manner. Molecular analysis PLCζ gene patient with deficiency has previously identified point mutation causing histidine proline substitution at residue 398 (PLCζH398P), leading abnormal Ca2+ release...
The extracellular calcium-sensing receptor CaSR is expressed in blood vessels where its role not completely understood. In this study, we tested the hypothesis that vascular smooth muscle cells (VSMC) directly involved regulation of pressure and vessel tone. Mice with targeted gene ablation from were generated by breeding exon 7 LoxP-CaSR mice animals which Cre recombinase driven a SM22α promoter (SM22α-Cre). Wire myography performed on Cre-negative [wild-type (WT)] Cre-positive Δflox/Δflox...
Stimuli that increase calcium or NAADP may promote proton release from the endosomes and lysosomes by activating TPC1.
Anti-apoptotic Bcl-2 proteins are upregulated in different cancers, including diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL), enabling survival by inhibiting pro-apoptotic Bcl-2-family members inositol 1,4,5-trisphosphate (IP3) receptor (IP3R)-mediated Ca2+-signaling. A peptide tool (Bcl-2/IP3R Disruptor-2; BIRD-2) was developed to abrogate the interaction of with IP3Rs targeting Bcl-2′s BH4 domain. BIRD-2 triggers cell death primary CLL cells DLBCL lines....
Pancreatic β cells are electrically excitable and respond to elevated glucose concentrations with bursts of Ca2+ action potentials due the activation voltage-dependent channels (VDCCs), which leads exocytosis insulin granules. We have examined possible role nicotinic acid adenine dinucleotide phosphate (NAADP)-mediated release from intracellular stores during stimulus-secretion coupling in primary mouse pancreatic cells. NAADP-regulated channels, likely two-pore (TPCs), recently been shown...
Two-pore channels (TPCs) have been recently identified as NAADP-regulated Ca(2+) release channels, which are localized on the endolysosomal system. TPCs a 12-transmembrane domain (TMD) structure and evolutionary intermediates between 24-TMD α-subunits of Na(+) or transient receptor potential channel superfamily, six TMDs in single subunit form tetramers with 24 active channels. Based this relationship, it is predicted that dimerize to functional but dimerization human has so far not studied....
Abstract The induction of olfactory preferences by larval and early adult experience for odour from wheat or maize grain was examined the granary weevil Sitophilus granarius L. in a static four‐chamber olfactometer. Weevils were reared on either received different experience. It turned out that weevils isolated as pupae kernels preferred olfactometer when they emerged without any presence odour. both When normally adults kernel which developed, avoided. In contrast, no found most...
Abstract Encapsulation of nanoparticles (NPs) in polymeric nanofibers is an effective way controlling physicochemical properties such as stability and integrity. In this study, bioavailable ferritin‐like NPs, previously demonstrated to be treatment for iron deficiency anemia (IDA), are encapsulated successfully the pH‐sensitive polymer Eudragit L100 through modification electrospinning configuration reversal conventional input voltage. Transmission electron microscopy (TEM) these show IHAT...
Abstract Background Androgen deprivation therapy (ADT) is the treatment of choice for metastatic prostate cancer (PCa). After an initial response to ADT, PCa cells can generate castration resistant (CRPC) or neuroendocrine (NEPC) malignancies, which are incurable. T‐type calcium channels (TTCCs) emerging as promising therapeutic targets several cancers, but their role in progression has never been investigated. Methods To examine TTCCs PCa, we analyzed expression level, copy number variants...
Small-molecule fluorescent Ca 2+ reporters are the most widely used tools in field of signaling. The excellent spatial and temporal resolution afforded by has driven understanding as a messenger many different cell types. In situations, cellular loading monitoring indicators is quite trivial. However, there numerous pitfalls that require consideration to ensure optimal data recorded. Fluorescent have carboxylic acid groups for binding . Because these “free-acid” forms hydrophilic they cannot...