Source: ImmunoDB
CTLs: C-Type Lectins
Summary

Mike Osta

Kafatos/Christophides Group, Faculty of Natural Sciences, Division of Cell and Molecular Biology, Imperial College London, UK

Glycans, complex polymers of sugar units that decorate proteins and lipids, have various biological roles in the development, growth, function or survival of an organism. Many of the roles ascribed to glycans involve specific recognition by lectins, carbohydrate-binding proteins of ubiquitous nature. Perhaps the largest and most diverse family of animal lectins is the C-type lectins (CTLs) which are Ca+-dependent proteins that function largely outside the cells and are either secreted or membrane-bound [Drickamer & Taylor 1993]. Sugar-binding activity of CTLs is usually ascribed to a single module designated a CRD (carbohydrate-recognition domain), which forms a subset of a large family of protein modules that are denoted C-type lectin-like domains (CTLDs) many of which are Ca+-independent and bind to non-sugar ligands [Drickamer & Fadden 2002]. Invertebrate CTLs mediate several immune responses including opsonisation and microbial clearance [Jomori & Natori 1992; Yu & Kanost 2003], hemocyte nodule formation [Koizumi et al. 1999] and activation of prophenoloxidase leading to melanization [Chen et al. 1995; Yu et al. 1999; Yu & Kanost 2000]. Two CTLs from Ag were shown to be negative regulators of ookinete melanization, while they lacked regulatory impact on Sepadex bead melanization, indicating a potential specialized immune evasive function for Plasmodium [Osta et al. 2004; Warr et al. in press]. Phylogenetic analysis of Ag, Aa and Dm immunity-realated genes identified 25, 39 and 34 CTLs, respectively. Interestingly 9 clear 1:1:1 orthologues exist between the three species. The Aa orthologue of AgCTL7 and CG1576 was partially identified; Blasting the Aa contigs with AgCTL7 identified exons 3 and 4 of AaCTL7 however exons 1 and 2 of the gene could not be found possibly due to an error in gene assembly in that region. As a result AaCTL7 was not included in the phylogenetic analysis. Those genes conserved in all three species may be implicated in conserved developmental processes. Only one of these genes, furrowed,(CG1500) has been functionally studied in Dm and showed indeed to be required for the proper development of the Dm eye and mechanosensory bristles [Leshko-Lindsay & Corces 1997]. There was only 1 orthologous pair (AgCTL8 and AaCTL8) for which no Dm orthologue could be identified. Several species-specific family expansions exist. The largest one is in Aa and includes 20 genes. A Dm expansion includes 14 genes all of which, except one (CG7763), are clustered on chromosome 2L. The Ag expansion includes 5 potential mannose binding CTLs, all of which are clustered within 12 kb at 2L/25D. Interestingly, an Aa CTL (AaCTLMA14) showed strong sequence homology to AgCTL4, which was shown to inhibit P. berghei ookinete melanization in Ag. While these genes could not be considered 1:1 orthologues as the relevant bootstrap support was not strong enough, their striking sequence homology within and outside the CRD domains suggests that they might have similar functions. Interestingly, AgCTL4 clusters also with AgCTLMA2 both in the tree as well as on chromosome 2L/21F suggesting that these parasite agonists originated by gene duplication followed by diversification.