Glycolipids: Structure and Function

The sugar units of glycan structures store information and establish an alphabet of life. The language of the oligosaccharide coding units is deciphered by receptors such as lectins and the decoded message can be transduced by multiple signaling pathways. Similar to glycoconjugates, these receptors can exhibit pronounced changes in quantitative and qualitative aspects of expression, as attested by a wealth of lectin and immunohistochemical studies. Since histochemistry provides a static picture, it is essential to shed light on the mechanisms of how a recognitive protein-carbohydrate interplay can be transduced into cellular responses. Their consequences for example for cell morphology will then be visible to the histochemist. Therefore, basic signaling routes will be graphically outlined and their trigger potential will be explained by selected examples from the realm of glycosciences.

Section: Mitogenic and Apoptotic Effects Of Lectinsmentioning

confidence: 99%

Signaling Pathways for Transduction of the Initial Message of the Glycocode into Cellular Responses

Villalobo

Gabius

1998

“…The past 5 years have seen an enormous proliferation of research studies documenting the breadth and depth of glycobiology in all facets of development and differentiation [Gabius, 1997a;Kopitz, 1997;Varki, 1998]. These studies have used the latest and most sophisticated research tools and techniques, including molecular probes and recombinant technology, whose sensitivity and specificity stagger the imagination.…”

Section: Introductionmentioning

confidence: 99%

Glycocoding as an Information Management System in Embryonic Development

Mann¹,

Waterman²

1998

The past 5 years have seen a burgeoning in the amount of data emerging from laboratories studying the early stages of embryogenesis. Much of this data implicates various aspects of glycobiology in the initiation and regulation of these processes. The level of analytical detail coming from these investigations has surpassed our ability to fully understand its overall significance within the context of the interactive/dynamic developmental process. This review proposes a pause in this seemingly endless quest for more detail so that we may take stock of our goals and objectives. The proposed goals include a mechanistic understanding of the process(es) involved in information managed at various ‘transition points’ during early embryogenesis, and an understanding of the mechanism(s) by which the spatial/temporal regulation of early development are managed. The ‘transitions’ which occur during cell to cell cluster, cell cluster to early organ architecture, and early organ architecture to functional organ development are fundamental and mirror the evolutionary process of biological information management. All of these ‘transitions’ involve increasing complexity, the development of hierarchies of information management systems (integrated bidirectionally), and spatial/temporal regulation which relies on historical events to map future structure and function. This review focuses on a relatively small number of studies which highlight these aspects of early development. A mechanism which involves glycocoding, an extension of the Roseman Hypothesis, and its direct use as an information management system is proposed and some supporting experimental evidence is presented. This extension of an existing hypothesis is related to several recent investigations, and is designed to broaden the experimental design of future studies so that these important process issues can be addressed.

“…4) and on glycolipids [Kopitz, 1997;Reuter and Gabius, 1999], the complexity of the carbohydrate chains will encompass structural code words from the sugar alphabet especially at the spatially accessible nonreducing tips of antennae [Varki, 1996;Hooper et al, 1997;Reuter and Gabius, 1999]. Their accessibility contributes to turn them into suitable partners for intermolecular contact.…”

Section: Lectins: the Link Between Sugar Code And Cellular Responsementioning

confidence: 99%

“…In view of the notable fraction of the genome devoted to the production of the large array of enzymes assigned to glycan assembly [Brockhausen and Schachter, 1997;Sears and Wong, 1998;Kapitonov and Yu, 1999] it is reassuring that this investment into carrier modification will not be futile but can lead to functional relevance [Roseman, 1970;Marshall, 1972;Winterburn and Phelps, 1972;Berger et al, 1982;Olden et al, 1982;Sharon, 1984Sharon, , 1998Varki, 1993;Cook, 1994;Kopitz, 1997;Rudd and Dwek, 1997;Sharon and Lis, 1997;Mann and Waterman, 1998;Reuter and Gabius, 1999]. Indeed, the growing appreciation of the concept to consider oligosaccharides as information-storing coding units is reflected in the term 'sugar code' [Laine, 1997;Gabius, 2000].…”

Section: Introductionmentioning

confidence: 99%

Towards Defining the Role of Glycans as Hardware in Information Storage and Transfer: Basic Principles, Experimental Approaches and Recent Progress

Solı́s¹,

Jiménez‐Barbero²,

Kaltner³

et al. 2000

The term ‘code’ in biological information transfer appears to be tightly and hitherto exclusively connected with the genetic code based on nucleotides and translated into functional activities via proteins. However, the recent appreciation of the enormous coding capacity of oligosaccharide chains of natural glycoconjugates has spurred to give heed to a new concept: versatile glycan assembly by the genetically encoded glycosyltransferases endows cells with a probably not yet fully catalogued array of meaningful messages. Enciphered by sugar receptors such as endogenous lectins the information of code words established by a series of covalently linked monosaccharides as letters for example guides correct intra- and intercellular routing of glycoproteins, modulates cell proliferation or migration and mediates cell adhesion. Evidently, the elucidation of the structural frameworks and the recognition strategies within the operation of the sugar code poses a fascinating conundrum. The far-reaching impact of this recognition mode on the level of cells, tissues and organs has fueled vigorous investigations to probe the subtleties of protein-carbohydrate interactions. This review presents information on the necessarily concerted approach using X-ray crystallography, molecular modeling, nuclear magnetic resonance spectroscopy, thermodynamic analysis and engineered ligands and receptors. This part of the treatise is flanked by exemplarily chosen insights made possible by these techniques.