Distribution and Function of Lectins in Organisms

 If we accept the scenario on the origin of glycans and their diversification by bricolage, as mentioned at the beginning of this chapter (ES-00), lectins for recognizing glycans may represent part of the scenario and possibly have some “deviation” in their distribution and function (specificity) in organisms. For example, lectins that recognize glucose and mannose (aldohexoses which constitute the first triplet in the above scenario) are assumed to function for fundamental biological activities because these saccharides are believed to be older than the other saccharides. In contrast, lectins that recognize late-comer saccharides, such as galactose, sialic acid, etc. (explainable as bricolage products derived from glucose and mannose), function for relatively limited activities in higher and more complicated life forms. This scheme, however, may not be applied to every lectin, and is limited to proving the link between the evolution of glycans and the evolution of life.

Lectins number approximately twenty families including carbohydrate recognition domains in enzymes (the domains in enzymes of carbohydrate recognition that mediate binding to target molecules, CRD), whereas lectin proteins are known to have a variety of structures. About ten families of lectins in animals have been well studied, as shown in Figure 1. With progress in genome analysis, homologous genes have been revealed to exist in model organisms other than humans, renewing attention from the viewpoint of relationship between structure and function. For example, Prof. Drickamer et al. ( claim that more than 120 C-type lectin genes (LE-A04) exist in the nematode (Caenorhabditis elegans), which is a model organism representing multicellular animals and has been analyzed earlier than others. More than 10 galectins (LE-A01), which are lectins that recognize -galactoside, are known to exist in the worm, and have been analyzed for their functionality to some extent. Since glycoconjugates are not well understood, we do not know to what extent the processing capability of complex type N-linked oligosaccharides is preserved in these invertebrates and vertebrates including humans. They are, however, presumably galectins that function as receptors, represented by galactose recognition, specifically existing in multicellular organisms due to the fact that no homologue genes have been found yet in yeast. Further, siglecs are pointed out as typical lectins specific to higher animals. This lectin family belongs to the immunoglobulin superfamily of proteins (classified into an I-type lectin family) and has functions specific to vertebrates (LE-B04), such as a variety of cell-signal controls, specific recognition of sialylated oligosaccharides, etc. The siglecs are understood to have proliferated rapidly at a latter stage of evolution, due to the fact that the siglecs are poorly homologous among species and almost all siglecs cluster themselves at a same place on chromosomes. In contrast, R-type lectins (LE-A08) are pointed out as common lectins (CRD) among microorganisms. The lectins, named after a ricin B-chain, often function as an AB-type toxin and a subdomain in enzymes. Ricin, which is a plant toxin, is specific to galactose and is obviously targeted in animal cells, whereas the lectin CRD, distributed in a vast range of organisms, shows a variety of specificity to sialic acid, mannose, xylose, etc., together with galactose. An R-type lectin domain exists, almost without exception, at the C-terminal of peptide-N-acetyl-galactosaminyltransferases (ppGalNAcT) that catalyze the first step of muchin-type oligosaccharides synthesis (transfer N-acetyl-galactosamin (GalNAc) to a polypeptide chain), and contributes to form a muchin cluster. Sambucus sieboldiana lectin (SSA) and Sambucus nigra lectin (SNA) that are known as representative lectins specific for sialic acid, belong to the R-type lectin family. It can not be denied, as of now, that the genes of these lectins spread by the horizontal gene transfer from prokaryotes to eukaryotes, or vice versa, though the R-type lectins, which show specificity to a variety of glycans and are abundant in organisms, seem to have nothing to do with the relationship between the origin of glycans and evolution which is proposed here.
 Figure 1. Phylogenic distribution of various types of lectins and varieties of their basic monosaccharide specificities
On the other hand, calnexin and calreticulin (ES-B01), which are related to the folding of glycoproteins, are lectins that recognize a non-reducing-end glucose residue in an N-linked oligosaccharide precursor, and are likely to possess same specificity and functionality among all eukaryotes that are understood based on the universality of the biosynthesis mechanism on N-linked oligosaccharides, whereas a calnexin gene in yeast has not been proved to function for this purpose. In the same way, there are a variety of lectins that exist in cells and are abundant in multicellular organisms: VIP36 and ERGIC53 (ES-C04) that are mannose-specific lectins as cargo receptors, EDEM-relating M-type lectins that are homologues to -mannosidase but have no catalytic activity, and two homologous lectins (cation-dependent or -independent mannose-6-phosphate-binding lectins) that recognize mannose-6-phosphate, a well-studied target tag for lysosomal enzymes. These lectins in cells have specificity to either glucose or mannose and are supposed to have arisen at the earliest stage of evolution. This observation implies that the origin of carbohydrates is certainly related to evolution.

The above suggests, though not strongly, that some relationship exists between distribution of lectins in organisms and common functionality, and between specificity and locality inside or outside cells. Comparative glycomics tries to understand glycans in their basic structure and mechanism from the viewpoint of biological evolution. Such studies may not lead to function analyses of glycans or to industrial applications. Nevertheless, we cannot escape the issue of evolution in science, because we all seek the answer to the question, “How did we get here?” Glycans, even though they are not directly governed by genes, should not be ignored.
Jun Hirabayashi (Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology (AIST))
References (1) Taylor ME, Drickamer K: “Introduction to Glycobiology”, Oxford University Press (Oxford), 2003
(2) Drickamer K, Dodd RB: C-Type lectin-like domains in Caenorhabditis elegans: predictions from the complete genome sequence. Glycobiology, 9, 1357-1369, 1999
(3) Cooper DN, Barondes SH: God must love galections; he made so many of them. Glycobiology, 9, 979-984, 1999
Dec. 28, 2004

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