A5085537512- Glycosylation and Glycoproteins Research
- Galectins and Cancer Biology
- Carbohydrate Chemistry and Synthesis
- Chemokine receptors and signaling
- Monoclonal and Polyclonal Antibodies Research
- Receptor Mechanisms and Signaling
- Peptidase Inhibition and Analysis
- Immunotherapy and Immune Responses
- Neuropeptides and Animal Physiology
- Ubiquitin and proteasome pathways
- Protease and Inhibitor Mechanisms
- Alzheimer's disease research and treatments
- Metabolism, Diabetes, and Cancer
- Adipose Tissue and Metabolism
- Invertebrate Immune Response Mechanisms
- Congenital Heart Disease Studies
- 14-3-3 protein interactions
- Cell Adhesion Molecules Research
- Signaling Pathways in Disease
- Diabetes Treatment and Management
- Genetic and Kidney Cyst Diseases
- Advanced Proteomics Techniques and Applications
- Congenital heart defects research
- RNA modifications and cancer
- T-cell and B-cell Immunology
University of Copenhagen
2013-2024
Beth Israel Deaconess Medical Center
2020-2023
Harvard University
2020-2023
Beth Israel Deaconess Hospital
2023
Significance Ectodomain shedding is a central event in range of biological processes and pathways, however the underlying mechanisms are still not fully understood. Here we present evidence that site-specific O-glycosylation regulated by individual GalNAc-Transferase isoforms, serve to coregulate ectodomain shedding, predominantly through blocking cleavage. Our general finding exemplified specific role single GalNAc-T isoform (GalNAc-T2) coregulating TNF-alpha release vitro, ex vivo isogenic...
The low-density lipoprotein receptor (LDLR) and related receptors are important for the transport of diverse biomolecules across cell membranes barriers. Their functions especially relevant cholesterol homeostasis diseases, including neurodegenerative kidney disorders. Members LDLR-related protein family share LDLR class A (LA) repeats providing binding properties lipoproteins other biomolecules. We previously demonstrated that short linker regions between these LA contain conserved O-glycan...
Peptide hormones and neuropeptides encompass a large class of bioactive peptides that regulate physiological processes like anxiety, blood glucose, appetite, inflammation pressure. Here, we execute focused discovery strategy to provide an extensive map O-glycans on peptide hormones. We find almost one third the 279 classified carry O-glycans. Many identified O-glycosites are conserved predicted serve roles in proprotein processing, receptor interaction, biodistribution biostability....
Atrial natriuretic peptide (ANP) is a hormone that in response to atrial stretch secreted from myocytes into the circulation, where it stimulates vasodilatation and natriuresis. ANP an important biomarker of heart failure low plasma concentrations exclude cardiac dysfunction. member (NP) family, which also includes B-type (BNP) C-type peptide. The proforms these hormones undergo processing mature peptides, for proBNP, this process has previously been demonstrated be regulated by...
Abstract Studies on the expression of cellular glycans are limited by a lack sensitive tools that can discriminate specific structural features. Here we describe development robust platform using immunized lampreys ( Petromyzon marinus ), which secrete variable lymphocyte receptors called VLRBs as antibodies, for generating libraries anti-glycan reagents. We identified wide variety glycan-specific detectable in lamprey plasma after immunization with whole fixed cells, tissue homogenates, and...
Chemokine ligands and receptors regulate the directional migration of leukocytes. Post-translational modifications chemokine including O-glycosylation tyrosine sulfation have been reported to ligand binding resulting signaling. Through in silico analyses, we determined potential conserved sites on human murine CC receptors. Glyco-engineered CHO cell lines were used measure impact receptor CCR5, while mutation residues treatment with sodium chlorate performed determine effect sulfation....
Abstract The terminal galactose residues of N- and O-glycans in animal glycoproteins are often sialylated and/or fucosylated, but sulfation, such as 3-O-sulfated (3-O-SGal), represents an additional, poorly understood modification. To this end, we have developed a novel sea lamprey variable lymphocyte receptor (VLR) termed O6 to explore 3-O-SGal expression. was engineered recombinant murine IgG chimera its specificity affinity the epitope defined using variety approaches, including glycan...
Complex carbohydrates serve a wide range of biological functions in cells and tissues, their biosynthesis involves more than 200 distinct glycosyltransferases (GTfs) human cells. The kinetic properties, cellular expression patterns subcellular topology the GTfs direct glycosylation capacity cell. Most are ER or Golgi resident enzymes, specific localization is believed to be distributed secretory pathway according sequential role process, although detailed knowledge for individual enzymes...
The endogenous chemokines CCL19 and CCL21 signal via their common receptor CCR7. is the main lymph node homing chemokine, but a weak chemo-attractant compared to CCL19. Here we show that 41-amino acid positively charged peptide, released through C-terminal cleavage of CCL21, C21TP, boosts immune cell recruiting activity by up 25-fold signaling CCR7 ~ 100-fold. Such boosting unprecedented. Despite presence multiple basic glycosaminoglycan (GAG) binding motifs, C21TP does not involve...
ABSTRACT The sorting receptor sorLA encoded by the SORL1 gene is implicated in Alzheimer’s disease (AD) pathogenesis. Genetic studies have identified AD-associated mutations and expression of AD brains reported to be reduced. SorLA a retromer trafficking complex functions at endosome, deficiency phenocopies endosomal pathologies found AD. undergoes posttranslational modifications maturation with ultimate ectodomain shedding, however knowledge these processes remains limited. Here we...
N-terminal nonsynonymous single-nucleotide polymorphisms (SNPs) of G protein-coupled receptors (GPCRs) are common and often affect receptor post-translational modifications. Their functional implications are, however, largely unknown. We have previously shown that the human β