A5040017166- Glycosylation and Glycoproteins Research
- Carbohydrate Chemistry and Synthesis
- Galectins and Cancer Biology
- Proteoglycans and glycosaminoglycans research
- Cellular transport and secretion
- Genetic Associations and Epidemiology
- Trace Elements in Health
- Monoclonal and Polyclonal Antibodies Research
- Lysosomal Storage Disorders Research
- Drug Transport and Resistance Mechanisms
- Virus-based gene therapy research
- Diabetes and associated disorders
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Endoplasmic Reticulum Stress and Disease
- Immune Response and Inflammation
- Pancreatic function and diabetes
- Proteins in Food Systems
- Ubiquitin and proteasome pathways
- Biochemical and Structural Characterization
- Food composition and properties
- Caveolin-1 and cellular processes
- Biochemical and Molecular Research
- Diet, Metabolism, and Disease
- Toxin Mechanisms and Immunotoxins
Hadassah Medical Center
2024
Beth Israel Deaconess Medical Center
2020-2024
Harvard University
2020-2024
L'Institut Agro
2024
Physiologie Environnement et Génétique pour l'Animal et les Systèmes d'Elevage
2024
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
2024
Université de Lille
2016-2023
Centre National de la Recherche Scientifique
2016-2023
Unité de Glycobiologie Structurale et Fonctionnelle
2016-2023
Abstract Glycosylation is essential to brain development and function, but prior studies have often been limited a single analytical technique excluded region- sex-specific analyses. Here, using several methodologies, we analyze Asn-linked Ser/Thr/Tyr-linked protein glycosylation between regions sexes in mice. Brain N-glycans are less complex sequence variety compared other tissues, consisting predominantly of high-mannose fucosylated/bisected structures. Most O-glycans unbranched,...
Sialylation of glycoproteins and glycolipids is catalyzed by sialyltransferases in the Golgi mammalian cells, whereby sialic acid residues are added at nonreducing ends oligosaccharides. Because sialylated glycans play critical roles a number human physio-pathological processes, past two decades have witnessed development modified derivatives for better understanding biology new therapeutic targets. However, nothing known about how individual tolerate behave towards these unnatural...
Pea cell walls have been shown to encapsulate nutrients inside cells, thereby limiting their hydrolysis by digestive enzymes. However, it is unknown how the wall performs this barrier function. In particular, could be due presence of specific polysaccharides or, most probably, organisation components within wall. This study aimed investigate prevented protein hydrolysis. To address objective, isolated cells were obtained using different treatments thought affect differently (incubations in...
Glycosylation, a common modification of cellular proteins and lipids, is often altered in diseases pathophysiological states such as hypoxia, yet the underlying molecular causes remain poorly understood. By utilizing lectin microarray glycan profiling, Golgi pH redox screens, we show here that hypoxia inhibits terminal sialylation N- O-linked glycans HIF- independent manner by lowering oxidative potential. This state change was accompanied loss two surface-exposed disulfide bonds catalytic...
Mutations in genes encoding molecular chaperones can lead to chaperonopathies, but none have so far been identified causing congenital disorders of glycosylation. Here we two maternal half-brothers with a novel chaperonopathy, impaired protein O-glycosylation. The patients decreased activity T-synthase (C1GALT1), an enzyme that exclusively synthesizes the T-antigen, ubiquitous O-glycan core structure and precursor for all extended O-glycans. function is dependent on its specific chaperone...
Protein O-glycosylation is a critical modification in the brain, as genetic variants pathway are associated with common and severe neuropsychiatric phenotypes. However, little known about most abundant O-glycans mammalian which N-acetylgalactosamine (O-GalNAc) linked. Here, we determined spatial localization, protein carriers, cellular function of O-GalNAc glycans mouse brain. We observed striking enrichment neuronal tracts, specifically at nodes Ranvier, specialized structures involved...
FUT8-CDG is a severe multisystem disorder caused by mutations in FUT8, encoding the α-1,6-fucosyltransferase. We report on dizygotic twins with presenting dysmorphisms, failure to thrive, and respiratory abnormalities. Due phenotype, oral L-fucose supplementation was started. Glycosylation analysis using mass spectrometry indicated limited response fucose therapy while clinical presentation stabilized. Further research needed assess concept of substrate FUT8-CDG.
Mammalian sialyltransferases transfer sialic acids onto glycoproteins and glycolipids within the Golgi apparatus. Despite their key role in glycosylation, study of enzymatic activities is limited by lack appropriate tools. Herein, we developed a quick sensitive sialyltransferase microplate assay based on use unnatural CMP-SiaNAl donor substrate. In this assay, an acceptor glycoprotein coated bottom 96-well plate activity assessed using CMP-SiaNAl. The alkyne tag SiaNAl enables subsequent...
GlycA is a nuclear magnetic resonance (NMR) signal in plasma that correlates with inflammation and cardiovascular outcomes large data sets. The thought to originate from N-acetylglucosamine (GlcNAc) residues of branched N-glycans, though direct experimental evidence limited. Trace element concentrations affect glycosylation patterns may thereby also influence GlycA.NMR was measured samples 87 individuals correlated MALDI-MS N-glycomics trace analysis. We further evaluated the genetic...
Gangliosides are glycosphingolipids concentrated in glycolipid-enriched membrane microdomains. Mainly restricted to the nervous system healthy adult, complex gangliosides such as GD3 and GD2 have been shown be involved aggressiveness metastasis of neuro-ectoderm derived tumors melanoma neuroblastoma. synthase (GD3S), key enzyme that controls biosynthesis gangliosides, was over-expressed Estrogen Receptor (ER)-negative breast cancer tumors, associated with a decreased overall survival...
Natural and synthetically modified cytidine monophosphate activated sialic acids (CMP-Sias) are essential research assets in the field of glycobiology: among other applications, they can be used to probe glycans, detect sialylation defects at cell surface or carry out detailed studies sialyltransferase activities. However, these chemical tools notoriously unstable because hydrolytic decomposition, very time-consuming costly obtain. They nigh impossible store with satisfactory purity, their...
The Sda /Cad antigen reported on glycoconjugates of human tissues has an increasingly recognized wide impact the physio-pathology different biological systems. last step its biosynthesis relies enzymatic activity β1,4-N-acetylgalactosaminyltransferase-II (B4GALNT2), which shows highest expression level in healthy colon. Previous studies occurrence colonic cells two B4GALNT2 protein isoforms that differ length their cytoplasmic tail, long isoform showing extended 66-amino acid tail. We...
Abstract The human polysialyltransferases ST8Sia II and IV catalyze the transfer of several Neu5Ac residues onto glycoproteins forming homopolymers with essential roles during different physiological processes. In salmonids, heterogeneous set sialic acids polymers have been described in ovary on eggs cell surface three genes st8sia4, st8sia2-r1 st8sia2-r2 were identified that could be implicated these heteropolymers. from salmonid Coregonus maraena cloned, recombinantly expressed HEK293...
Abstract The development and function of the brain requires N-linked glycosylation proteins, which is a ubiquitous modification in secretory pathway. N-glycans have distinct composition undergo tight regulation brain, but spatial distribution these structures remains relatively unexplored. Here, we systematically employed carbohydrate binding lectins with differing specificities to various classes appropriate controls identify glycan expression multiple regions mouse brain. Lectins...
The mammalian mono-α2,8-sialyltransferase ST8Sia VI has been shown to catalyze the transfer of a unique sialic acid residues onto core 1 O-glycans leading formation di-sialylated O-glycosylproteins and lesser extent diSia motifs glycolipids like GD1a. Previous studies also reported identification an orthologue ST8SIA6 gene in zebrafish genome. Trying get insights into biosynthesis function oligo-sialylated glycoproteins during development, we cloned studied this fish α2,8-sialyltransferase...
Abstract Hepatocytes synthesize a vast number of glycoproteins found in their membranes and secretions, many which contain O-glycans linked to Ser/Thr residues. As the functions distribution on hepatocyte-derived membrane blood are not well understood, we generated mice with targeted deletion Cosmc (C1Galt1c1) hepatocytes. Liver WT express typical sialylated core 1 (T antigen/CD176) (Galβ1-3GalNAcα1-O-Ser/Thr), whereas knockout hepatocytes (HEP-Cosmc-KO) lack extended Tn antigen (CD175)...
We identified and analyzed α2,8-sialyltransferases sequences among 71 ray-finned fish species to provide the first comprehensive view of Teleost ST8Sia repertoire. This repertoire expanded over course Vertebrate evolution was primarily shaped by whole genome events R1 R2, but not Teleost-specific R3. showed that duplicated st8sia genes like st8sia7, st8sia8, st8sia9 have disappeared from Tetrapods, whereas their orthologues were maintained in Teleosts. Furthermore, several specific...
Summary Glycosylation is essential to brain development and function, though prior studies have often been limited a single analytical technique. Using several methodologies, we analyzed Asn-linked (N-glycans) Ser/Thr/Tyr-linked (O-glycans) protein glycosylation between regions sexes in mice. Brain N-glycans were surprisingly less complex sequence variety compared other tissues, consisting predominantly of high-mannose precursors fucosylated/bisected structures. Most O-glycans unbranched,...
ABSTRACT Protein N-linked glycosylation is a ubiquitous modification in the secretory pathway that plays critical role development and function of brain. N-glycans have distinct composition undergo tight regulation brain, but spatial distribution these structures remains relatively unexplored. Here, we systematically employed carbohydrate binding lectins with differing specificities to various classes appropriate controls identify multiple regions mouse Lectins high-mannose-type N-glycans,...
Abstract Protein O-glycosylation is a critical modification in the brain, as genetic variants pathway are associated with both common and severe neuropsychiatric phenotypes. However, little known about most abundant type of O-glycan mammalian which O-GalNAc linked. Here, we determined spatial localization, protein carriers, cellular function glycans mouse brain. We observed striking enrichment white matter tracts at nodes Ranvier. Glycoproteomic analysis revealed that more than half...
The synapse is an essential connection between neuronal cells in which the membrane and secreted glycoproteins regulate neurotransmission. post-translational modifications of with carbohydrates, although for their functions as well specific localization, are not understood. Oddly, whereas galactose addition to required functions, galactosylation severely restricted Asn-linked on N-glycans brain, genetic evidence highlights important roles brain development. To explore this novel...
Abstract The protein glycome of individual cell types in the brain is unexplored, despite critical function these modifications development and disease. In aggregate, most abundant asparagine (N-) linked glycans adult are high mannose structures, specifically Man 5 GlcNAc 2 (Man-5), which normally exits ER for further processing Golgi. Mannose structures uncommon other organs often overlooked or excluded studies. To understand cell-specific contributions to unique N-glycome its abundance...
Abstract A missense mutation (A391T) in the manganese transporter SLC39A8 is strongly associated with schizophrenia genomic studies, though molecular connection to brain remains hypothetical. Human carriers of A391T have reduced serum manganese, altered plasma glycosylation, and MRI changes consistent metal transport. Here, using a knock-in mouse model homozygous for A391T, we show that schizophrenia-associated variant protein glycosylation brain. N-linked was most significantly impaired,...