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Galectins Experimental Protocols and Unsolved Questions (Narratives)

Editor/ Jun Hirabayashi, Sachiko Sato

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On the origin of galectin and galactose –Part 2–

Jun Hirabayashi

last updated 2022/08/01 (Glycoforum. 2022 Vol.25 (4), A9)  
DOI: https://doi.org/10.32285/glycoforum.25A9

In the preceding chapter (Part 1), the authors described the origin of galectins while focusing on the point that galectins are essentially cytosolic proteins1. In this chapter, one of the authors (J.H.) hypothesizes that the presence of carbohydrates is prerequisite to the generation of lectins that recognize them as counterpart molecules, and that the presence of galactose (the carbohydrate ligand of galectin) is prerequisite to the generation of galectin. Clearly, the question is: what is the origin of galactose? In this chapter and as previously proposed by Hirabayashi (for details, see refs. 1-4), a hypothesis regarding the “late arrival of galactose” and the origin of saccharides is presented. ...and more

On the origin of galectin and galactose –Part 1–

Jun Hirabayashi / Ryuichiro Suzuki

last updated 2022/06/01 (Glycoforum. 2022 Vol.25 (3), A6)  
DOI: https://doi.org/10.32285/glycoforum.25A6

Galectins are characterized as a group of evolutionarily related proteins having a conserved unique sequence with the ability to bind galactose (rigorously to bind β-galactoside). To date, their diverse biological distributions and functions have been described; however, the origin of galectin has only scarcely been discussed. Curiously, all of them so far investigated lack a signal sequence required for secretion, while they are assumed to function in extracellular spaces, where a vast amount of galectin-binding glycans exist. In fact, regardless of biological species, all the galectins are biosynthesized as “cytosolic proteins”. This suggests that they have intrinsic functions in the cytosol. In this chapter (Part 1), we describe the origin of galectins in light of their cytosolic features. In the following chapter (Part 2), We attempt to discuss the most fundamental issues of galactose, to which all galectins bind, by referring to the origins of monosaccharides and their chirality. ...and more

The galectin-lattice: a decoder of bio-equivalent glycans

Haik Mkhikian / Michael Sy / James W. Dennis / Michael Demetriou

last updated 2021/08/01 (Glycoforum. 2021 Vol.24 (4), A10)  
DOI: https://doi.org/10.32285/glycoforum.24A10

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. ...and more

Milk oligosaccharides and galectins: Spin-off version - from a glycoscience point of view

Why does breast milk contain a large amount of “galectin stripper”, milk oligosaccharides? What is their mysterious function?

Junko Nio-Kobayashi / Tadasu Urashima / Jun Hirabayashi / Sachiko Sato

last updated 2021/10/01 (Glycoforum. 2021 Vol.24 (5), A13)  
DOI: https://doi.org/10.32285/glycoforum.24A13

The binding affinity of lectins for glycans is generally displayed at the µM level; however, milk contains more than 10 mM oligosaccharides and 100 mM lactose. Such an astonishingly high concentration of glycans present in milk could inhibit the binding of most endogenous lectins to their glycan ligands. Then, many questions naturally arise, for example: what is the biological significance of the inhibitory activity? How high are the milk oligosaccharide concentrations in the digestive tract, and what is the pharmacokinetics of milk oligosaccharides in the body?
In this spin-off version, we try to present our guesses or “daydream” – our extended speculation – and discuss about how milk oligosaccharides are used once they enter the body, what roles they may play, and what their relationship may be to the function of galectins, which are abundant in the digestive tract. In addition, we reconsider the reason why mammals have acquired the ability to biosynthesize lactose and use it as a nutrient source for babies, which is said to be the “key to the evolutionary success of mammals”. ...and more

Milk oligosaccharides and galectins: Spin-off version - from a glycoscience point of view

Do milk oligosaccharides get altered under breeding conditions? An underlying mechanism for structural conversion and diversification

Tadasu Urashima / Sachiko Sato / Junko Nio-Kobayashi / Jun Hirabayashi

last updated 2021/08/01 (Glycoforum. 2021 Vol.24 (4), A11)  
DOI: https://doi.org/10.32285/glycoforum.24A11

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?...and more

Milk oligosaccharides and galectins: Spin-off version - from a glycoscience point of view

Wobbling of substrate recognition caused by a molecular switch in the lactose synthase β4Gal-T1

Tadasu Urashima / Sachiko Sato / Junko Nio-Kobayashi / Jun Hirabayashi

last updated 2021/06/01 (Glycoforum. 2021 Vol.24 (3), A6)  
DOI: https://doi.org/10.32285/glycoforum.24A6

This chapter is a “spin-off” version of “Milk oligosaccharides and Galectins” by Urashima and Hirabayashi, published in the main part of the Galectin series (Vol. 24 [2], A3). Here, we chose a few topics that could not be fully dealt with in the main chapter, thereby aiming to advance discussions about important, but unsolved questions of milk oligosaccharides, in a free and active forum with the extended members. We hope you will enjoy this new forum style. ...and more

Milk oligosaccharides and galectins

Tadasu Urashima / Jun Hirabayashi

last updated 2021/04/01 (Glycoforum. 2021 Vol.24 (2), A3)  
DOI: https://doi.org/10.32285/glycoforum.24A3

Mammalian milk or colostrum usually contains a variety of milk oligosaccharides in addition to lactose (Galβ1-4Glc) as the predominant saccharide. Almost all of them have a lactose unit at their reducing ends and also contain galactose (Gal), N-acetylglucosamine (GlcNAc), fucose (Fuc), N-acetyl or N-glycolylneuraminic acid (Neu5Ac and Neu5Gc, respectively), or N-acetylgalactosamine (GalNAc) residues. For example, human milk contains more than 250 varieties of oligosaccharides at a concentration of 12–13 g/L (see Note 1). Around 170 of the more than 250 chemical structures have been characterized to date.1 In this chapter of the series, the potential utilization of milk oligosaccharides is discussed as a unique research tool to solve the unanswered questions related to galectins. ...and more

In memory of Professor Hans-Joachim Gabius

last updated 2021/9/26 (Glycoforum)  

Galectins: (much) more than ga(lactose-binding)lectins

Hans-Joachim Gabius

last updated 2021/02/01 (Glycoforum. 2021 Vol.24 (1), A1)  
DOI: https://doi.org/10.32285/glycoforum.24A1

Lectins have a central role in translating glycan-encoded information into bioactivity. They are classified according to the fold of their carbohydrate recognition domain (CRD). This structural unit is proposed to be capable to do (much) more than to interact with cognate glycan(s). As outlined for the proof-of-principle case of the galectin CRD, distinct sequence elements appear capable to extend a CRD’s functionality profile: they can implement molecular switches for activity, conformation and quaternary structure, even establish complementary regions for other types of binding partners, letting the CRD gain an unsuspected multifunctionality. By further testing and validating these suggestions, answers may be provided for major unresolved questions, e.g. why galectins belong to the small set of secreted proteins without a signal sequence. This case study teaches the salient lesson of the possibility for a CRD to consist of various structural elements beyond that binding the sugar. Of potential relevance for public health, the idea of a gene capture from the host as origin of viral adhesins that have a galectin-like fold (incl. coronaviruses such as SARS-CoV-2) may inspire innovative modalities to counter pandemic threats. ...and more

The Keyhole of Galectin is Made Loose, and the Inserted Key Easily Comes Out

Kenichi Kasai

last updated 2020/12/01 (Glycoforum. 2020 Vol.23 (6), A17)  
DOI: https://doi.org/10.32285/glycoforum.23A17

Galectin is a well-known molecular entity but remains difficult to understand. Although it appears on a wide variety of stages, it is seldom the main actor; its role seems to be supporting but indispensable. It acts with a wide variety of partners whatever their identity (protein, lipid, or proteoglycan) or position, as long as they are wearing a favorite costume (glycan). Therefore, almost all (more than 10,000) extracellular proteins can be its partners, although its relationships with them are not so intimate. This wide and shallow sociality makes the essential nature of galectin difficult to understand. With these aspects in mind, I would like to review some basic points concerning galectin and its weak interactions. ...and more

A note on expression and purification of recombinant galectins(Glycoforum. 2020 Vol.23 (5), A15)
Nozomu Nishi
Introduction to Galectins
Experimental Protocols and Unsolved Questions (Narratives)(Glycoforum. 2020 Vol.23 (5), A14)
Jun Hirabayashi / Sachiko Sato
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