A5101662784- Cellular Mechanics and Interactions
- Cell Adhesion Molecules Research
- Receptor Mechanisms and Signaling
- Cellular transport and secretion
- Advanced Fluorescence Microscopy Techniques
- Protein Kinase Regulation and GTPase Signaling
- Microtubule and mitosis dynamics
- Lipid Membrane Structure and Behavior
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Phagocytosis and Immune Regulation
- S100 Proteins and Annexins
- Chemokine receptors and signaling
- T-cell and B-cell Immunology
- Photosynthetic Processes and Mechanisms
- CRISPR and Genetic Engineering
- Mitochondrial Function and Pathology
- Viral Infectious Diseases and Gene Expression in Insects
- Erythrocyte Function and Pathophysiology
- Neurobiology and Insect Physiology Research
- Protist diversity and phylogeny
- Monoclonal and Polyclonal Antibodies Research
- Retinal Development and Disorders
- Bacterial Genetics and Biotechnology
- Glycosylation and Glycoproteins Research
- Evolution and Genetic Dynamics
Fujian Medical University
2025
East China University of Science and Technology
2024
National Institute of Allergy and Infectious Diseases
2015-2024
National Institutes of Health
2015-2024
Government of the United States of America
2022
Fisher College
2020
Southern University of Science and Technology
2018
University of Electronic Science and Technology of China
2018
University of Groningen
2018
Johns Hopkins University
1995-2017
Receptor-mediated activation of heterotrimeric GTP–binding proteins (G-proteins) was visualized in living Dictyostelium discoideum cells by monitoring fluorescence resonance energy transfer (FRET) between α- and β- subunits fused to cyan yellow fluorescent proteins. The G-protein heterotrimer rapidly dissociated reassociated upon addition removal chemoattractant. During continuous stimulation, reached a dose-dependent steady-state level. Even though physiological responses subsided, the did...
Gradients of chemoattractants elicit signaling events at the leading edge a cell even though chemoattractant receptors are uniformly distributed on surface. In highly polarized Dictyostelium discoideum amoebas, membrane-associated betagamma subunits heterotrimeric guanine nucleotide-binding proteins (G proteins) were localized in shallow anterior-posterior gradient. A applied generated binding sites for pleckstrin homology (PH) domains inner surface membrane pattern similar to that...
The chemokine CXCL12 and its G-protein-coupled receptor CXCR4 control the migration, invasiveness metastasis of breast cancer cells. Binding to triggers activation heterotrimeric Gi proteins that regulate actin polymerization migration. However, pathways linking receptor/Gi signalling cell migration are not known. Here we show stimulation promotes interaction between Gαi2 ELMO1. ELMO1 both required for CXCL12-mediated polymerization, invasion a Gαi2-dependent membrane translocation ELMO1,...
Oxidative stress and reactive oxygen species (ROS) can elicit modulate various physiological pathological processes, including cell death. However, the mechanisms controlling ROS-induced death are largely unknown. Data from this study suggest that receptor-interacting protein (RIP) tumor necrosis factor receptor (TNFR)-associated 2 (TRAF2), two key effector molecules of TNF signaling, essential for We found RIP(-/-) or TRAF2(-/-) mouse embryonic fibroblasts (MEF) resistant to when compared...
The signaling network underlying eukaryotic chemosensing is a complex combination of receptor-mediated transmembrane signals, lipid modifications, protein translocations, and differential activation/deactivation membrane-bound cytosolic components. As such, it provides particularly interesting challenges for combined computational experimental analysis. We developed novel detailed molecular model that, when used to simulate the response attractant cyclic adenosine monophosphate (cAMP), made...
Chemotaxis and phagocytosis are basically similar in cells of the immune system Dictyostelium amebae. Deletion unique G protein β subunit D. discoideum impaired but had little effect on fluid-phase endocytosis, cytokinesis, or random motility. Constitutive expression wild-type restored normal development. Chemoattractants released by bacteria trigger typical transient actin polymerization responses cells. In subunit–null cells, a series point mutants, these were to degree that correlated...
Activation of G-protein-coupled chemoattractant receptors triggers dissociation Galpha and Gbetagamma subunits. These subunits induce intracellular responses that can be highly polarized when a cell experiences gradient chemoattractant. Exactly how achieves this amplified signal polarization is still not well understood. Here, we quantitatively measure temporal spatial changes receptor occupancy, G-protein activation by FRET imaging, PIP3 levels monitoring the dynamics PH(Crac)-GFP...
B cell responses are initiated by the clustering of receptor (BCR) binding multivalent antigens. Clustering leads to phosphorylation tyrosines in cytoplasmic domains BCR inner plasma membrane leaflet-associated Src-family kinase Lyn. At present, little is known about earliest events after that precede BCR's Here we use fluorescence resonance energy transfer (FRET) living cells detect interaction with a Lyn-based membrane-targeted reporter first several seconds clustering. The results showed...
Suppressor of fused (Sufu) is an essential negative regulator the sonic hedgehog (Shh) pathway, but little known about how Sufu itself normally regulated. Here, we report that phosphorylated at Ser-342 and Ser-346 by GSK3β cAMP-dependent protein kinase A (PKA), respectively, phosphorylation this dual site stabilizes against Shh signaling-induced degradation. We further show localization in primary cilium induced signaling required for turnover both total Sufu. Perturbing with PKA inhibitors...
Abstract IL-17 and its receptor are founding members of a novel inflammatory cytokine family. To date, only one subunit has been identified, termed IL-17RA. All known receptors consist complex multiple subunits. Although IL-17-family cytokines exist as homodimers, the configuration stoichiometry IL-17R remain unknown. We used fluorescence resonance energy transfer (FRET) to determine whether IL-17RA subunits multimerize, and, if so, they preassembled in plasma membrane. HEK293 cells...
Introduction Ochratoxin A (OTA) is a toxic secondary metabolite produced by Aspergillus and Penicillium species, posing significant threat to global food safety. Previous studies have demonstrated the diverse effects of OTA, including hepatotoxicity, nephrotoxicity, carcinogenicity. However, limited understanding exists regarding its immunotoxicity underlying mechanisms, particularly in relation innate immunity. Methods Zebrafish embryos were exposed varying concentrations OTA assess impact...
Mesaconitine (MA), a predominant diterpenoid alkaloid isolated from Aconitum species, exhibits notable pharmacological properties but is simultaneously associated with significant toxicological concerns, its hepatotoxic mechanisms remaining largely unelucidated. In this study, zebrafish embryos were systematically exposed to MA investigate effects on hepatic development and function. Comprehensive analyses of liver morphology, inflammatory response, oxidative stress, apoptotic pathways...
The connection between calcium oscillation and cell sensitivity is poorly understood. Calcium triggered either spontaneously or upon receptor-ligand binding. cytosolic [Ca2+] increase during initiated from Ca2+ release the intracellular stores through phospholipase C (PLC)-derived inositol 1,4,5-trisphosphate (IP3). Here, we show that neutrophils lacking PLCg2 display impaired spontaneous chemoattractant-induced response, decreased membrane targeting of CAPRI (a RasGAP), subsequent increased...
Valproic acid (VPA) is used to treat epilepsy and bipolar disorder prevent migraine. It also undergoing trials for cancer therapy. However, the biochemical molecular biological actions of VPA are poorly understood. Using social amoeba Dictyostelium discoideum, we show that an acute effect inhibition chemotactic cell movement, a process partially dependent upon phospholipid signaling. Analysis this shows attenuates signal-induced translocation PH(Crac)-green fluorescent protein from cytosol...
Gprotein–coupled receptor (GPCR) signaling mediates a balance of excitatory and inhibitory activities that regulate Dictyostelium chemosensing to cAMP. The molecular nature kinetics these inhibitors are unknown. We report transient cAMP stimulations induce PIP3 responses without refractory period, suggesting GPCR-mediated inhibition accumulates decays slowly. Moreover, exposure gradients leads asymmetric distribution the components. stable accumulation reporter PHCrac-GFP in front cells near...
Chemotaxis requires precisely coordinated polymerization and depolymerization of the actin cytoskeleton at leading fronts migrating cells. However, GPCR activation-controlled F-actin remains largely elusive. Here, we reveal a novel signaling pathway, including Gαi, PLC, PKCβ, protein kinase D (PKD), SSH2, in control cofilin phosphorylation cytoskeletal reorganization, which is essential for neutrophil chemotaxis. We show that PKD chemotaxis GPCR-mediated activation depends on PLC/PKC...
Cells display chemotaxis and electrotaxis by migrating directionally in gradients of specific chemicals or electrical potential. Chemotaxis Dictyostelium discoideum is mediated G protein-coupled receptors. The unique Gbeta essential for all chemotactic responses, although different chemoattractants use receptors Galpha subunits. amoebae show striking an applied direct current electric field. Perhaps share similar signaling mechanisms? Null mutation cAMP receptor 1 Galpha2 did not abolish...
Inhibition of NK cell cytotoxicity by killer Ig-like receptors (KIR) depends on phosphorylation cytoplasmic tyrosines in KIR, which recruit tyrosine phosphatase Src homology protein 1. It is not clear how whose function lies downstream a kinase, succeeds blocking proximal activation signals upon binding HLA class I target cells. Here we show that mixing cells with insect expressing HLA-C was sufficient to induce clustering and KIR SHP-1. Transient detected the presence pervanadate, an...