A5035139800- Cellular transport and secretion
- Lipid metabolism and biosynthesis
- Advanced Fluorescence Microscopy Techniques
- Retinal Development and Disorders
- Endoplasmic Reticulum Stress and Disease
- Mitochondrial Function and Pathology
- Microtubule and mitosis dynamics
- Cell Image Analysis Techniques
- Adipose Tissue and Metabolism
- Single-cell and spatial transcriptomics
- Lipid Membrane Structure and Behavior
- Nerve injury and regeneration
- Plant tissue culture and regeneration
- Peroxisome Proliferator-Activated Receptors
- Alzheimer's disease research and treatments
- Antioxidant Activity and Oxidative Stress
- Photosynthetic Processes and Mechanisms
- Axon Guidance and Neuronal Signaling
- Ferroptosis and cancer prognosis
- Plant Physiology and Cultivation Studies
- Neurogenesis and neuroplasticity mechanisms
- Plant biochemistry and biosynthesis
- Plant Virus Research Studies
- Ubiquitin and proteasome pathways
- Edible Oils Quality and Analysis
University of Alberta
2019-2024
McGill University
2011-2024
Women and Children’s Health Research Institute
2019-2024
Cyprus Institute of Neurology and Genetics
2021-2023
Montreal Neurological Institute and Hospital
2011-2023
Howard Hughes Medical Institute
2017-2019
Janelia Research Campus
2017-2019
Helix (United States)
2017
Imaging Center
2017
McMaster University
2017
Lipid droplets (LDs) are neutral lipid storage organelles that transfer lipids to various including peroxisomes. Here, we show the hereditary spastic paraplegia protein M1 Spastin, a membrane-bound AAA ATPase found on LDs, coordinates fatty acid (FA) trafficking from LDs peroxisomes through two interrelated mechanisms. First, Spastin forms tethering complex with peroxisomal ABCD1 promote LD–peroxisome contact formation. Second, recruits membrane-shaping ESCRT-III proteins IST1 and CHMP1B via...
Significance Multiple studies have implicated dozens of risk loci that may be associated with Alzheimer’s disease (AD), but common mechanisms underlying how they contribute to onset or progression remain elusive. This study identifies cell-specific roles for Drosophila orthologs AD genes in lipid droplet formation that, when disrupted, lead neurodegeneration. Our work reinforces a critical role the sequestration peroxidated lipids glia, and places Apolipoprotein E ε4 (APOE4) other factors...
Pathogen-mediated activation of macrophages arms innate immune responses that include enhanced surface ruffling and macropinocytosis for environmental sampling receptor internalization signaling. Activation with bacterial lipopolysaccharide (LPS) generates prominent dorsal ruffles, which are precursors macropinosomes. Very rapid, high-resolution imaging live lattice light sheet microscopy (LLSM) reveals new features actions redefine the process macropinosome formation closure. We offer a...
Our ability to unambiguously image and track individual molecules in live cells is limited by packing of multiple copies labeled within the resolution limit. Here we devise a universal genetic strategy precisely control copy number fluorescently cell. This system has dynamic range ∼10,000-fold, enabling sparse labeling proteins expressed at different abundance levels. Combined with photostable labels, this extends duration automated single-molecule tracking two orders magnitude. We...
The small guanosine triphosphatase Rab13 functions in exocytic vesicle trafficking epithelial cells. Alterations activity have been observed human cancers, yet the mechanism of activation and its role cancer progression remain unclear. In this paper, we identify DENN domain protein DENND2B as guanine nucleotide exchange factor for develop a novel Förster resonance energy transfer–based Rab biosensor to reveal by at leading edge migrating interacts with effector MICAL-L2 cell periphery,...
Nerve growth factor (NGF) promotes the survival and differentiation of neurons. NGF is initially synthesized as a precursor, proNGF, which predominant form in central nervous system. proNGF bind to TrkA/p75NTR mediate cell sortilin/p75NTR promote apoptosis. The ratio TrkA p75NTR affects whether mature signal or purpose this study was determine loss influences sortilin expression levels, establish have similar ability switch between death. We systematically altered receptor levels by priming...
During oxidative stress neurons release lipids that are internalized by glia. Defects in this coordinated process play an important role several neurodegenerative diseases. Yet, the mechanisms of lipid and its consequences on neuronal health unclear. Here, we demonstrate lipid-protein particle autolysosome exocytosis protects from ferroptosis, a form cell death driven peroxidation. We show during stress, peroxidated iron released autolysosomal which requires exocytic machinery VAMP7 syntaxin...
Intercellular transmission of α-synuclein contributes to Parkinson's disease pathology. Yet, the mechanisms spread are not fully understood. Here, we used live-cell microscopy examine impact associated lipid alterations on release. We discovered that increased glucosylceramides induce ectosome shedding from primary neurons, and dopaminergic neurons derived patient iPSCs harboring mutations in GBA1 (N370S, L444P W378G) LRRK2 (G2019S R1441H) compared their isogenic control. show elevated...
ApoE mediates the transport of lipids from neurons to glial lipid droplets. ApoE4, a major risk factor for Alzheimer's disease, impairs this pathway, increasing neurodegeneration. ApoE2 and ApoE3 Christchurch (ApoE3Ch) variants confer resistance developing yet little is known regarding how these protective affect transport. Here, we explored lipoprotein particles containing different isoforms neuronal health in vitro intact rodent hippocampi. We demonstrate that ApoE3Ch protect ferroptosis...
Available data suggest that genetic as well environmental factors may influence nuts and seeds nutrients content. In this context cultivated in Greece were studied. Macronutrients content was agreement with from other areas. Total phenolics the range of 43.0 ± 2.1-1512.7 60.7 mg GAE/100 g for chestnut walnut, respectively. Thirteen to 22 individual identified studied species. Oleanolic acid 0.10-9.03 mg/100 g. Pumpkin contained higher squalene (71.6 g). β-Sitosterol predominated all samples...
The small GTPase Rab35 regulates endosomal membrane trafficking but also recruits effectors that modulate actin assembly and organization. Differentially expressed in normal neoplastic cells (DENN)-domain proteins are a newly identified class of Rab guanine-nucleotide exchange factors (GEFs) grouped into eight families, each activating common Rab. members one family, connecdenn 1-3/DENND1A-C, all GEFs for Rab35. Why requires multiple is unknown. We demonstrate 3 uses unique C-terminal motif,...
Coatomer (COPI)-coated vesicles mediate membrane trafficking in the early secretory pathway. There are at least three subclasses of COPI coats and two classes Arf GTPases that couple coat proteins to membranes. Whether mechanisms exist link specific Arfs subcomplexes is unknown. We now demonstrate Scy1-like protein 1 (Scyl1), a member family catalytically inactive kinases, oligomerizes through centrally located HEAT repeats uses C-terminal RKXX-COO(-) motif interact directly with appendage...
Abstract Neurons and glia operate in a highly coordinated fashion the brain. Although glial cells have long been known to supply lipids neurons via lipoprotein particles, new evidence reveals that lipid transport between is bidirectional. Here, we describe co‐culture system study transfer of lipid‐associated proteins from glia. The assay entails culturing on separate coverslips, pulsing with fluorescently labeled fatty acids, then incubating coverslips together. As astrocytes internalize...
The purpose of this study was to evaluate the neuroprotective effects omega-3 polyunsaturated fatty acid (ω3-PUFA) supplementation in a mouse model OPA1-associated autosomal dominant optic atrophy (ADOA). blood level arachidonic (AA) and eicosapentaenoic (EPA) served adjust treatment dosage (AA/EPA = 1.0–1.5). Eight-month-old mice were allocated four groups (n 20/group): ω3-PUFA-treated Opa1enu/+, untreated wild-type groups. Treated received ω3-PUFAs, EPA docosahexaenoic (DHA; 5:1 ratio) by...