Paradigms for glycan-binding receptors in cell adhesion
Introduction
Ever since the diversity of carbohydrates found on mammalian cell surfaces was recognised, it has been speculated that unique combinations of sugars on individual cells might form the basis for specific cell adhesion events [1]. Proteins able to bind to these glycans present a plausible mechanism for specific recognition events, in which a glycan-binding receptor on one cell interacts with glycans on another cell [2]. However, in many cases, the role of glycan–receptor interaction may be to modulate adhesion rather than to provide a simple bridge between cells (Figure 1). In reviewing the current state of this field, with particular emphasis on progress in the past two years, it is now possible to set high standards for evidence implicating specific receptor–glycan interactions in cell adhesion. The focus of this review will be on mammalian adhesion systems, evaluating which potential adhesion systems are understood in molecular detail and which are supported by convincing physiological evidence about how they function.
Section snippets
Selectins in normal and tumour cell adhesion
The selectins remain the best characterised glycan-binding receptors with well-defined roles in cell adhesion [3, 4]. Experimental approaches ranging from X-ray crystallography to analysis of knockout mice have documented how selective interactions of the selectins with glycoprotein ligands bearing glycans terminating in the sialyl-Lewisx or sialyl-Lewisa tetrasaccharides lead to transient adhesion between leukocytes and endothelia (see Figure 2 for a summary of key glycan structures). Although
Identification of blood cell glycoprotein ligands for DC-SIGN
While the function of the selectins as cell adhesion molecules is now well documented, the importance of other glycan-binding receptors in cell adhesion, as opposed to clearance of pathogens or turnover of serum glycoproteins, remains less well understood. One receptor with a particularly ambiguous dual function is DC-SIGN, which was originally named as a cell adhesion receptor, Dendritic Cell Specific Intercellular adhesion molecule 3-Grabbing Nonintegrin, but which has been more extensively
The scavenger receptor C-type lectin: a novel endothelial receptor that binds Lewisx
The scavenger receptor C-type lectin (SRCL) is a hybrid surface molecule on endothelial cells that, like other scavenger receptors, is organised as extended rod-like domains composed of coiled-coils of α-helices adjacent to collagen-like helices [21, 22]. SRCL is unique amongst the scavenger receptor family in having a carbohydrate-recognition domain at the distal end of the rod domains. Screening of a glycan array with SRCL revealed that it shows unusually selective binding to only a few
A role for galectins in endothelial cell interactions
The galectins are soluble glycan-binding proteins that have been proposed to link cells to each other and to the extracellular matrix by virtue of their bivalency (Figure 1). Some galectins achieve bivalency as a result of dimerisation of a constituent polypeptide that contains a single carbohydrate-recognition domain, while in other galectins two binding sites are adjacent to each other in a single polypeptide [26, 27]. The valance of galectin-3, one of the most extensively studied of the
Polysialic acid and regulation of adhesion in the nervous system
Another known modifier of cell adhesion is polysialic acid, which is attached to a select set of proteins, including the neural cell adhesion molecule (NCAM) [32]. A major effect of polysialylation is to inhibit cell adhesion in general rather than to interfere directly with specific adhesive interactions. Molecular force and other measurements have been used to validate the hypothesis that the charge on extended polysialic acid chains causes increased repulsion between apposing membranes, and
Conclusions
On the basis of the structures of glycan-binding receptors known to be expressed on cell surfaces, it is possible to screen genomes to identify additional receptors (www.imperial.ac.uk/research/animallectins). Such a genomic analysis suggests that the number of human glycan-binding receptors in the three main lectin groups is less than 50 (Table 1). Of these, only a few have at least partially documented roles in cell adhesion even in two of the most complex multicellular situations, the immune
References and recommended reading
Papers of particular interest, published within the annual period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgement
This work was supported by grant 075565 from the Wellcome Trust.
References (40)
Reflection on glycobiology
J Biol Chem
(2001)Glycan-dependent leukocyte adhesion and recruitment in inflammation
Curr Opin Cell Biol
(2003)- et al.
Carbohydrate-mediated cell adhesion in cancer metastasis and angiogenesis
Cancer Sci
(2004) - et al.
A distinct glycoform of CD44 is an L-selectin ligand of human hematopoietic cells
Proc Natl Acad Sci USA
(2000) - et al.
Carbohydrate profiling identifies new pathogens that interact with dendritic cell-specific ICAM-3-grabbing nonintegrin on dendritic cells
J Immunol
(2003) - et al.
CEACAM1, an adhesion molecule of human granulocytes, is fucosylated by fucosyltransferase IX and interacts with DC-SIGN of dendritic cells via Lewis x residues
Glycobiology
(2006) - et al.
DC-SIGN binds ICAM-3 isolated from peripheral human leukocytes through Lewis x residues
Glycobiology
(2007) - et al.
Scavenger receptor C-type lectin binds to the leukocyte cell surface glycan Lewis x by a novel mechanism
J Biol Chem
(2007) - et al.
God must love galectins; He made so many of them
Glycobiology
(1999) - et al.
Galectin-1: a small protein with major functions
Glycobiology
(2006)
Direct evidence that neural cell adhesion molecule (NCAM) polysialylation increases intermembrane repulsion and abrogates adhesion
J Biol Chem
A novel α-helix in the first fibronectin type III repeat of the neural cell adhesion molecule is critical for N-glycan polysialylation
J Biol Chem
Use of polysialic acid in repair of the central nervous system
Proc Natl Acad Sci USA
Myelin-associated glycoprotein (MAG): past, present and beyond
J Neurochem
History of lectins: from hemagglutinins to biological recognition molecules
Glycobiology
Ligands for L-selectin: homing, inflammation, and beyond
Annu Rev Immunol
A major class of L-selectin ligands is eliminated in mice deficient in two sulfotransferases expressed in high endothelial venules
Nat Immunol
Flow-enhanced adhesion regulated by a selectin interdomain hinge
J Cell Biol
Glycoprotein glycosylation and cancer progression
Biochim Biophys Acta
Selectin ligand expression regulates the initial vascular interactions of colon carcinoma cells: the roles of CD44v and alternative sialofucosylated selectin ligands
J Biol Chem
Cited by (100)
Regeneration of Free Reducing Glycans from Reductive Amination-Tagged Glycans by Oxone
2022, Journal of Organic ChemistryRecognition of lipoproteins by scavenger receptor class A members
2021, Journal of Biological ChemistrySynthetic Carbohydrate Chemistry and Translational Medicine
2020, Journal of Organic Chemistry