A5022397275- Lipid Membrane Structure and Behavior
- Cellular transport and secretion
- Neuroscience and Neuropharmacology Research
- Erythrocyte Function and Pathophysiology
- Ion channel regulation and function
- Tissue Engineering and Regenerative Medicine
- Ion Channels and Receptors
- Receptor Mechanisms and Signaling
- Nanopore and Nanochannel Transport Studies
- Caveolin-1 and cellular processes
- Bacteriophages and microbial interactions
- Hemoglobin structure and function
- Alzheimer's disease research and treatments
- Lysosomal Storage Disorders Research
- Toxin Mechanisms and Immunotoxins
- Genetics and Neurodevelopmental Disorders
- Endoplasmic Reticulum Stress and Disease
- Pluripotent Stem Cells Research
- RNA Research and Splicing
- Neural dynamics and brain function
- Hippo pathway signaling and YAP/TAZ
- Neuroscience and Neural Engineering
- Cellular Mechanics and Interactions
- RNA regulation and disease
- Glycosylation and Glycoproteins Research
Duke-NUS Medical School
2009-2024
Nanyang Technological University
2022
University of Greenwich
2019-2022
Institute of Cancer Research
2018
Breast Cancer Now
2018
National University of Singapore
2008-2016
National Neuroscience Institute
2016
Stanford University
2003-2008
University of Geneva
1998-2007
The University of Queensland
1998
Stromal interaction molecule 1 (STIM1) has recently been identified by our group and others as an endoplasmic reticulum (ER) Ca(2+) sensor that responds to ER store depletion activates channels in the plasma membrane (PM). The molecular mechanism which STIM1 transduces signals from lumen PM is not yet understood. Here we developed a live-cell FRET approach show forms oligomers within 5 s after depletion. These rapidly dissociated when stores were refilled. We further formed before its...
Abnormal calcium signaling is a central pathological component of Alzheimer's disease (AD). Here, we describe the identification class compounds called ReS19-T, which are able to restore homeostasis in cell-based models tau pathology. Aberrant accumulation leads uncontrolled activation store-operated channels (SOCCs) by remodeling septin filaments at cell cortex. Binding ReS19-T septins restores filament assembly state and restrains entry through SOCCs. In amyloid-β tau-driven mouse disease,...
In this paper, we have investigated the effects of pore-forming toxin aerolysin, produced by Aeromonas hydrophila, on mammalian cells. Our data indicate that protoxin binds to an 80-kD glycosyl-phosphatidylinositol (GPI)-anchored protein BHK cells, and bound is associated with specialized plasma membrane domains, described as detergent-insoluble microdomains, or cholesterol-glycolipid “rafts.” We show then processed its mature form host cell proteases. propose preferential association rafts,...
Mutations in the leucine-rich repeat kinase 2 ( LRRK2 ) gene are currently recognized as most common genetic cause of parkinsonism. Among large number mutations identified to date, G2019S variant is common. In Asia, however, another variant, G2385R, appears occur more frequently. To better understand contribution different variants toward disease pathogenesis, we generated transgenic Drosophila over-expressing various human alleles, including wild type, G2019S, Y1699C, and G2385R LRRK2. We...
Background Pathological accumulation of cholesterol in late endosomes is observed lysosomal storage diseases such as Niemann-Pick type C. We here analyzed the effects NPC cells, or phenocopied by drug U18666A, on membrane organization and dynamics. Methodology/Principal Findings Cholesterol did not lead to an increase raft non-raft ratio anticipated. Strikingly, we a 2–3 fold size compartment. Most importantly, properties dynamics endosomal intralumenal vesicles were altered revealed reduced...
Aerolysin is secreted as an inactive dimeric precursor by the bacterium <i>Aeromonas hydrophila</i>. Proteolytic cleavage within a mobile loop near C terminus of protoxin required for oligomerization and channel formation. This contains sequence KVRRAR<sup>432</sup>, which should be recognized mammalian proprotein convertases such furin, PACE4, PC5/6A. Here we show that these three proteases cleave proaerolysin after Arg-432 <i>in vitro</i>, yielding active toxin. We also investigated...
The Ras/MAPK pathway regulates synaptic plasticity and cell survival in neurons of the central nervous system. Here, we show that KRas, but not HRas, acutely translocates from plasma membrane (PM) to Golgi complex early/recycling endosomes response neuronal activity. Translocation is reversible mediated by polybasic-prenyl targeting motif KRas. We provide evidence KRas translocation occurs through sequestration Ca2+/calmodulin (Ca2+/CaM) subsequent release PM, a process reminiscent GDP...
Cell migration during development and metastatic invasion requires the coordination of actin adhesion dynamics to promote protrusive activity at cell front. The knowledge molecular mechanisms required achieve such is fragmentary. Here we identify a new functional complex that drives motility. adaptor proteins ERC1a LL5 are with liprin-α1 for effective tumor invasion, do so by stabilizing Depletion either protein negatively affects on extracellular matrix, lamellipodial persistence, as well...
Recent findings point to a central role of the endoplasmic reticulum-resident STIM (Stromal Interaction Molecule) proteins in shaping structure and function excitatory synapses mammalian brain. The impact Stim genes on cognitive functions remains, however, poorly understood. To explore learning memory, we generated three mouse strains with conditional deletion (cKO) Stim1 and/or Stim2 forebrain. Stim1, Stim2, double Stim1/Stim2 cKO mice show no obvious brain structural defects or locomotor...
Parkinson's disease (PD) is a neurodegenerative disorder marked by the selective degeneration of dopaminergic neurons in nigrostriatal pathway. Several lines evidence indicate that mitochondrial dysfunction contributes to its etiology. Other studies have suggested alterations sterol homeostasis correlate with increased risk for PD. Whether these observations are functionally related is, however, unknown. In this study, we used toxin-induced mouse model PD and measured levels nine...
STIMs (STIM1 and STIM2 in mammals) are transmembrane proteins that reside the endoplasmic reticulum (ER) regulate store-operated Ca 2+ entry (SOCE). The function of brain is only beginning to be explored, relevance SOCE nerve cells being debated. Here we identify as a central organizer excitatory synapses. STIM2, but not its paralogue STIM1, influences formation dendritic spines shapes basal synaptic transmission neurons. We further demonstrate essential for cAMP/PKA-dependent...
Most mammalian cells have in their plasma membrane at least two types of lipid microdomains, non-invaginated rafts and caveolae. Glycosylphosphatidylinositol (GPI)-anchored proteins constitute a class that are enriched but not caveolae steady state. We analyzed the effects abolishing GPI biosynthesis on rafts, caveolae, cholesterol levels. GPI-deficient were obtained by screening for resistance to pore-forming toxin aerolysin, which uses this as receptors. Despite absence GPI-anchored...
Aerolysin is a pore-forming toxin that plays key role in the pathogenesis of <i>Aeromonas hydrophila</i>infections. In this study, we have analyzed effect aerolysin on human granulocytes (HL-60 cells). Proaerolysin could bind to these cells, was processed into active aerolysin, and led membrane depolarization, indicating are potential targets for toxin. Fura-2 measurements were used analyze cytosolic [Ca<sup>2+</sup>] homeostasis. As expected toxin, addition Ca<sup>2+</sup>influx across...
Primary human cells can be transformed into tumor by a defined set of genetic alterations including telomerase, oncogenic RasV12, and the suppressors p53 pRb. SV40 small T (ST) is required for anchorage-independent growth in vitro vivo. Here, we identify Hippo suppressor pathway as critical target ST cellular transformation. We report that uncouples YAP from inhibitory activity through PAK1-mediated inactivation NF2. Membrane-tethered activated PAK sufficient to bypass requirement growth....
Aerolysin is one of the major virulence factors produced by Aeromonas hydrophila, a human pathogen that produces deep wound infection and gastroenteritis. The toxin interacts with target mammalian cells binding to glycan core glycosylphosphatidyl inositol (GPI)-anchored proteins subsequently forms pore in plasma membrane. Since epithelial intestine are primary targets aerolysin, we investigated its effect on three types polarized cells: Caco-2 cells, derived from intestine; MDCK...
Self-amplification of phosphoinositide 3-kinase (PI3K) signaling is believed to regulate asymmetric membrane extension and cell migration, but the molecular organization underlying feedback circuit elusive. Here we use an inducible approach synthetically activate PI3K interrogate circuitry governing self-enhancement 3'-phosphoinositide (3-PI) signals in NIH3T3 fibroblasts. Synthetic activation initially leads uniform production 3-PIs at plasma membrane, followed by appearance highly...