A Family of Secreted Mucins from the Parasitic Nematode Toxocara canis Bears Diverse Mucin Domains but Shares Similar Flanking Six-cysteine Repeat Motifs

Abstract

Infective larvae of the parasitic nematode Toxocara canis secrete a family of mucin-like glycoproteins, which are implicated in parasite immune evasion. Analysis of T. canis expressed sequence tags identified a family of four mRNAs encoding distinct apomucins (Tcmuc-1-4), one of which had been previously identified in the TES-120 family of glycoproteins secreted by this parasite. The protein products of all four cDNAs contain signal peptides, a repetitive serine/threonine-rich tract, and varying numbers of 36-amino acid six-cysteine (SXC) domains. SXC domains are found in many nematode proteins and show similarity to cnidarian (sea anemone) toxins. Antibodies to the SXC domains of Tc-MUC-1 and Tc-MUC-3 recognize differently migrating members of TES-120. TES-120 proteins separated by chromatographic methods showed distinct amino acid composition, mass, and sequence information by both Edman degradation and matrix-assisted laser desorption ionization/time of flight mass spectrometry on peptide fragments. Tc-MUC-1, -2, and -3 were shown to be secreted mucins with real masses of 39.7, 47.8, and 45.0 kDa in contrast to their predicted peptide masses of 15.7, 16.2, and 26.0 kDa, respectively. The presence of SXC domains in all mucin products supports the suggestion that the SXC motif is required for mucin assembly or export. Homology modeling indicates that the sixcysteine domains of the T. canis mucins adopt a similar fold to the sea anemone potassium channel-blocking toxin BgK, forming three disulfide bonds within each subunit.

Caenorhabditis elegans Mutants Resistant to Attachment of Yersinia Biofilms

“…In the case of Srf, there is indirect evidence that the antigen recognized by monoclonal antibodies is an Olinked glycoprotein (Hemmer et al 1991), and this is consistent with the finding of mucin-like glycoproteins in a variety of nematode species (Gems and Maizels 1996;Loukas et al 2000;Theodoropoulos et al 2001). Again, the simplest model is that glycosylation defects in srf-3, bus-4, bus-12, and bus-17 mutants lead directly to loss or aberration of a glycan-containing epitope in the surface coat.…”

Toxocariasis: Clinical Aspects, Epidemiology, Medical Ecology, and Molecular Aspects

“…Presumably, the worms eventually die of old age. The fact that many of the excretory-secretory proteins from the juvenile stages constitute a family of at least six highly antigenic mucins (13) associated with the cuticular surface reinforces this concept (29). Secreted mucins temporarily coat the surface of the worm (43) and are shed into the host periodically (2).…”

Immune Responses in Hookworm Infections

“…SXC domains were first found in a lipid-binding protein in the infective larval surface coat of Toxocara canis (43), and the only homologs that could be found at the time were predicted proteins from C. elegans. SXC domains have since been identified in other nematode proteins, including mucins from T. canis tissue larvae (44,76,84), and in ESTs from B. malayi and over 70 ESTs from C. elegans, where they are found fused to metalloprotease and tyrosinase domains (15). The role of the SXC motif is unknown, but all nematode proteins containing this cassette possess a signal peptide (where the 5Ј end of the gene has been obtained), suggesting an extracellular role.…”