A5004339250- Ion Channels and Receptors
- Neurobiology and Insect Physiology Research
- Phytochemicals and Antioxidant Activities
- Photoreceptor and optogenetics research
- Geology and Paleoclimatology Research
- Ion channel regulation and function
- Geomagnetism and Paleomagnetism Studies
- Geological formations and processes
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- Cancer-related Molecular Pathways
- Neuroscience and Neural Engineering
- Plant Stress Responses and Tolerance
- Calcium signaling and nucleotide metabolism
- Pleistocene-Era Hominins and Archaeology
- Insect Pest Control Strategies
- Photochromic and Fluorescence Chemistry
- Erythrocyte Function and Pathophysiology
- bioluminescence and chemiluminescence research
- Geochemistry and Elemental Analysis
- Boron and Carbon Nanomaterials Research
- Advanced biosensing and bioanalysis techniques
- Histone Deacetylase Inhibitors Research
- Molecular Communication and Nanonetworks
- Biochemical Analysis and Sensing Techniques
Beijing Normal University
2016-2025
Jinan Central Hospital
2024
Shandong First Medical University
2024
Lanzhou University
2015-2023
Zaozhuang University
2019-2023
Nanjing University of Posts and Telecommunications
2023
China Pharmaceutical University
2023
Xiamen University
2020-2022
China Automotive Technology and Research Center
2022
Jiaozuo University
2004-2021
Calcium signals, pivotal in controlling cell function, can be generated by calcium entry channels activated plasma membrane depolarization or depletion of internal stores. We reveal a regulatory link between these two channel subtypes mediated the ubiquitous calcium-sensing STIM proteins. STIM1 activation store mutational modification strongly suppresses voltage-operated (Ca(V)1.2) while activating store-operated Orai channels. Both actions are short STIM-Orai region (SOAR) STIM1. interacts...
The application of current channelrhodopsin-based optogenetic tools is limited by the lack strict ion selectivity and inability to extend spectra sensitivity into near-infrared (NIR) tissue transmissible range. Here we present an NIR-stimulable platform (termed 'Opto-CRAC') that selectively remotely controls Ca2+ oscillations Ca2+-responsive gene expression regulate function non-excitable cells, including T lymphocytes, macrophages dendritic cells. When coupled upconversion nanoparticles,...
Oxidant stress influences many cellular processes, including cell growth, differentiation, and death. A well-recognized link between these processes oxidant is via alterations in Ca2+ signaling. However, precisely how oxidants influence signaling remains unclear. led to a phenotypic shift mobilization from an oscillatory sustained elevated pattern calcium release–activated (CRAC)–mediated capacitive entry, stromal interaction molecule 1 (STIM1)– Orai1-deficient cells are resistant stress....
Improved Navier–Stokes characteristic boundary conditions (NSCBC) are formulated for the direct numerical simulations (DNS) of laminar and turbulent counterflow flame configurations with a compressible flow formulation. The new scheme properly accounts multi-dimensional effects provides nonreflecting inflow outflow that maintain mean imposed velocity pressure, while substantially eliminating spurious acoustic wave reflections. Applications to various demonstrate proposed yield accurate...
Abstract Store-operated Ca 2+ entry mediated by STIM1 and ORAI1 constitutes one of the major routes in mammalian cells. The molecular choreography STIM1–ORAI1 coupling is initiated endoplasmic reticulum (ER) store depletion with subsequent oligomerization ER-luminal domain, followed its redistribution towards plasma membrane to gate channels. mechanistic underpinnings this inside-out signalling were largely undefined. By taking advantage a unique gain-of-function mutation within...
STIM proteins are sensors of endoplasmic reticulum (ER) luminal Ca(2+) changes and rapidly translocate into near plasma membrane (PM) junctions to activate entry through the Orai family highly Ca(2+)-selective "store-operated" channels (SOCs). Dissecting STIM-Orai coupling process is restricted by abstruse nature ER-PM junctional domain. To overcome this problem, we studied using chimera cytoplasmic C-terminal domains STIM1 STIM2 (S1ct S2ct) identifying a fundamental action powerful SOC...
Targeting epigenetic pathways is a promising approach for cancer therapy. Here, we report on the unexpected finding that targeting calcium signaling can reverse silencing of tumor suppressor genes (TSG). In screen drugs reactivate silenced gene expression in colon cells, found three classical targeted (DNA methylation and histone deacetylase inhibitors) 11 other induced methylated CpG island promoters driving reporter (GFP) as well endogenous TSGs multiple cell lines. These newly identified...
Abstract The ubiquitously expressed Orai Ca 2+ channels are gated through a unique process of intermembrane coupling with the -sensing STIM proteins. Despite significance Orai1-mediated signals, how gating Orai1 is triggered by STIM1 remains unknown. A widely held model invokes binding directly to pore-forming helix. Here we report that an C-terminal STIM1-binding site, situated far from N-terminal pore helix, alone provides trigger necessary and sufficient for channel gating. We identify...
Genetically encoded calcium indicators (GECIs) are indispensable tools for real-time monitoring of intracellular signals and cellular activities in living organisms. Current GECIs face the challenge suboptimal peak signal-to-baseline ratio (SBR) with limited resolution reporting subtle transients. We report herein development a suite sensors, designated NEMO, fast kinetics wide dynamic ranges (>100-fold). NEMO Ca2+ transients SBRs around 20-fold larger than top-of-the-range GCaMP6 series....
STIM1 and STIM2 are dynamic transmembrane endoplasmic reticulum Ca(2+) sensors, coupling directly to activate plasma membrane Orai entry channels. Despite extensive sequence homology, the STIM proteins functionally distinct. We reveal that short variable N-terminal random coil sequences of confer profoundly different activation properties. Using Orai1-expressing HEK293 cells, chimeric replacement 43-amino-acid N terminus with attenuates Orai1-mediated drastically slows store-induced Orai1...
Abstract The endoplasmic reticulum (ER) Ca 2+ sensor, STIM1, becomes activated when ER-stored is depleted and translocates into ER–plasma membrane junctions where it tethers activates Orai1 entry channels. dimeric STIM1 protein contains a small STIM-Orai-activating region (SOAR)—the minimal sequence sufficient to activate Since SOAR itself dimer, we constructed concatemer–dimers introduced mutations at F394, which critical for coupling activation. F394H mutation in both monomers completely...
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...
Abstract Stromal interaction molecule 1 (STIM1) monitors ER-luminal Ca 2+ levels to maintain cellular balance and support signalling. The prevailing view has been that STIM1 senses reduced ER through dissociation of bound from a single EF-hand site, which triggers dramatic loss secondary structure dimerization the luminal domain. Here we find domain 5–6 -binding sites, binding at these sites is energetically coupled controls switch second structured conformation rather than protein...
Depleting NAD+ by blocking its biosynthesis has emerged as an attractive anticancer strategy. Simultaneous blockade of production from the salvage and de novo synthesis pathways targeting NAMPT IDO1 could achieve more effective reduction and, subsequently, robust antitumor efficacy. Herein, we report discovery first series dual inhibitors according to multitarget drug rationales. Compound 10e good balanced inhibitory potencies against IDO1, significantly inhibits both proliferation migration...
STIM (stromal interaction molecule) and Orai, two recently identified protein families, mediate cellular Ca(2+) signals through a remarkably dynamic interaction. proteins are sensors of stored within the endoplasmic reticulum (ER). Orai highly selective plasma membrane (PM) channels that allow only ions to flow into cells. Although present in separate membranes, undergo profound reorganization culminating an exquisite pas de deux small junctional regions between ER PM. Before these can...
The Ca2+-sensing stromal interaction molecule (STIM) proteins are crucial Ca2+ signal coordinators. Cre-lox technology was used to generate smooth muscle (sm)-targeted STIM1-, STIM2-, and double STIM1/STIM2-knockout (KO) mouse models, which reveal the essential role of STIM in homeostasis their controlling function, growth, development cells (SMCs). Compared Cre+/– littermates, sm-STIM1-KO mice showed high mortality (50% by 30 d) reduced bodyweight. While sm-STIM2-KO without detectable...