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Lectin-glycan interactions: A meeting's harvest

Galectins, cell-surface galactoside-binding lectins, in cell-cell communication and signaling. Click here for a larger image. From Liu, F. T. & Rabinovich, G. A. Galectins as modulators of tumour progression. Nat. Rev. Cancer 5, 29–41 (2005).

The 23^rd Interlec meeting took place in Edinburgh and Stirling this year, and attracted 120 participants who discussed all aspects of lectin research in a remarkably friendly and cooperative atmosphere. Word limitations alone are responsible for me focusing here on only some of the many aspects of lectin-glycan interactions that were described in the keynote lectures.

Data presented in many of the talks re-enforced that lectin-glycan interactions orchestrate cellular fate. Importantly, the structural complexity of glycans offers many different ways for them to interact with lectins (Hans-Joachim Gabius). In neuroblastomas, the GM1 ganglioside is upregulated, and galectin-1 and -3 bind to different parts of the glycolipids. However, binding of galectin-1 inhibits cell proliferation, whereas the interaction between galectin-3 and GM1 inhibits galectin-1. Galectin-3 appears to be a key molecule in cancer development as it is used in the prognosis of advanced head and neck carcinoma (Karel Smetana). It also promotes transendothelial invasion of cancer cells by interaction with the MUC1 cell surface glycoprotein (Lu-Gang Yu).

Lymphocytes offer further impressive instances for the determination of cellular fate by lectin-glycan interactions. Galectin-1 interacts with T-cell glycans on CD45 and CD7 to form galectin-glycan lattices (Linda Baum). These lattices organize the cell membrane into membrane subdomains that transduce T-cell activation signals. Thus, instead of the notion that ligands "reach" their cell surface receptors and initiate a series of protein-protein interactions — also regulated by intracellular O-glycosylation — we are now beginning to understand that ligand binding is regulated by a complex network of galectin-glycan interactions. The presence of a sialic acid-binding immunoglobulin-like lectin such as sialoadhesin is a prerequisite for macrophages to attack opsonized erythrocytes (Paul Crocker); the sialoadhesin glycans, in turn, may interact with other lectins to modulate macrophage function.

Another block of lectures highlighted the fact that altered glycan composition — and, hence, altered lectin receptor usage — can be used as a disease signature (Jonathan Rhodes, Azita Alavi). Thirty-six different N-glycan structures have been identified on the two glycosylation positions of the IgG heavy chain, and it is fascinating that each of them can now be assigned to a different form of rheumatic disease.

The complexities of the receptor component of glycan-lectin interactions were vividly illustrated in talks about the mannose-binding lectin (MBL) — an important player in innate immunity (Peter Garred, Kazue Takahashi). Disrupting the formation of the MBL homooligomer leads to a higher incidence of infections in toddlers and reduces the life expectancy of CF patients. On the other hand, a high titre of wild-type MBL has been shown to increase the risk of cardiac conditions and decrease the infection-free time for HIV positive patients.

Apart from glycan-lectin interactions in disease, lectin receptors and their glycan ligands can also be used for tumor therapies. Lectins (agglutinins) from soybean and peanut have been used successfully to fractionate cells and to avoid graft-versus-host disease in stem cell transplantation (Nathan Sharon). Thirty years later the targeting of tumor-derived antigens to lectin receptors on dendritic cells affords activation and expansion of cytolytic CD8 T cells in cancer treatment (Yvette van Kooyk) — impressive illustrations of how the interplay between glycans and lectins can be harnessed for drug discovery.

Sadly, this report does not do justice to the many talks and posters identifying new lectins and highlighting lectin function in vertebrates and invertebrates, among them the characterization of galectins (Lecs) in Caenorhabditis elegans by Ken-Ichi Kasai's group. Their description of the Lec's glycan binding properties now opens the possibility for insight into their function in Caenorhabditis physiology and development through the use of Lec knockouts.

Interlec-23. 23^rd International Lectin Meeting, 11^th – 16^th July 2008. University of Stirling and University of Edinburgh. Webpage of the meeting; scientific programme.

Author: Mirko von Elstermann