Cell surface glycans are tissue-specific and developmentally regulated; therefore, they are used as markers of embryonic stem cells (ESCs) such as stage-specific embryonic antigens. However, the role of glycans in stem cells has not been fully elucidated. Therefore we performed an RNA interference (RNAi) screen for glycosyltransferases essential for self-renewal and pluripotency of mouse ESCs and identified the following four glycan structures that are required to maintain the naïve pluripotent state: (1) LacdiNAc structure (GalNAc β1,4GlcNAc), (2) heparan sulfate (HS), (3) O-GlcNAc, (4) T antigen (Galβ1,3GalNAc). They regulate the leukemia inhibitory factor (LIF), bone morphogenetic protein (BMP), and/or Wnt signals that act to maintain the naïve pluripotent state and/or the fibroblast growth factor 4 (FGF4) signal that triggers differentiation. Thus, various types of glycans regulate the stem cell status; these glycan structures are evolutionarily conserved from Drosophila to mammals. ...and more
The galectin lattice is a multi-valent interaction of galectins with glycoproteins at the cell surface that displays rapid exchange of binding partners with properties of liquid-liquid phase transitions, thereby acting as an intermediary between freely diffusing glycoproteins and stable complexes in the membrane. The galectin lattice (i) regulates flow of receptors and solute transporters to coated-pit endocytosis and/or caveolin domains, and (ii) promotes turnover of cell-cell contacts such as immune synapses and focal adhesion complexes. Metabolic regulation of UDP-GlcNAc supply to Golgi N-glycan remodeling regulates glycoprotein affinities for galectins –and in turn, trafficking and presentation at the cell surface. The lattice model has been validated in immune regulation, cancer progression and glucose homeostasis in mice. Here we review the interactions of metabolism, galectins and glycoprotein ligands as well as the utility of this model to predict and treat inflammation and autoimmunity.
In the main chapter of this series, “Milk oligosaccharides and galectins” (Glycoforum. 2021 Vol. 24 (2), A3), we commented that rat milk includes largely 3’-sialyllactose (3’-SL) and 6’-sialyllactose (6’-SL), while that of another rodent species, the lowland paca (Cuniculus paca), possesses more complex structures of milk oligosaccharides. This observation inspires us to postulate that the milk oligosaccharides of experimental animals are much simpler than those of wild animals. However, it was recently reported that rat and mouse milks contain a small amount of more complex oligosaccharides, such as sulfo 3’-sialyllactose. Here, we draw attention to another unsolved question as a theme for this second spin-off version: how is the structural diversity of milk oligosaccharides defined?
The recent COVID-19 pandemic is caused by a new coronavirus, SARS-CoV-2, whose spike protein on its surface binds to human cells via angiotensin-converting enzyme 2 (ACE2) receptors in the initial stage of infection. In that process, the structure of the spike protein changes from a “down-form” to an “up-form”, as demonstrated by cryo-electron microscopy. Biochemical experiments have shown that the surface of the spike protein is modified by many glycans. Glycans have been considered to play a role in protection against antibodies, i.e., immune evasion; however, how they contribute to the structural changes of the spike protein remains unclear. In this paper, we describe the role of glycans as elucidated by molecular dynamics simulation of the spike protein.
