Abstract
Lectins are non-immunoglobulin carbohydrate-binding proteins without enzymatic activity towards the bound carbohydrates. Many lectins of e.g. plants or fungi have been suggested to act as toxins to defend the host against predators and parasites. We have previously shown that the Coprinopsis cinerea lectin 2 (CCL2), which binds to α1,3-fucosylated N-glycan cores, is toxic to Caenorhabditis elegans and results in developmental delay and premature death. In this study, we investigated the underlying toxicity phenotype at the cellular level by electron and confocal microscopy. We found that CCL2 directly binds to the intestinal apical surface and leads to a highly damaged brush border with loss of microvilli, actin filament depolymerization, and invaginations of the intestinal apical plasma membrane through gaps in the terminal web. We excluded several possible toxicity mechanisms such as internalization and pore-formation, suggesting that CCL2 acts directly on intestinal apical plasma membrane or glycocalyx proteins. A genetic screen for C. elegans mutants resistant to CCL2 generated over a dozen new alleles in bre 1, ger 1, and fut 1, three genes required for the synthesis of the sugar moiety recognized by CCL2. CCL2-induced intestinal brush border defects in C. elegans are similar to the damage observed previously in rats after feeding the dietary lectins wheat germ agglutinin or concanavalin A. The evolutionary conserved reaction of the brush border between mammals and nematodes might allow C. elegans to be exploited as model organism for the study of dietary lectin-induced intestinal pathology in mammals.
Highlights
Lectins are carbohydrate-binding proteins without enzymatic activity towards the bound carbohydrates and are of non-immunoglobulin origin [1]
Coprinopsis cinerea lectin 2 (CCL2) is toxic to animals exposed at later developmental stages: whereas wild-type L4 larvae fed on control E. coli for 24 h matured into fertile adults, L4 animals fed on CCL2-expressing E. coli developed into thin, small, pale, sick young adults that had not yet laid any eggs (Fig 1B)
We describe the detailed pathology induced in C. elegans by CCL2, a fungal lectin that causes toxicity solely through its ability to bind to its glycotarget(s) on the intestinal apical surface
Summary
Lectins are carbohydrate-binding proteins without enzymatic activity towards the bound carbohydrates and are of non-immunoglobulin origin [1]. Apart from diverse internal biological functions in plants, fungi, and animals [1,2,3], lectins have been suggested to act as toxins
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