HIGH DIVERSITY IN MUCIN GENES AND MUCIN MOLECULES IN TRYPANOSOMA-CRUZI

Mucins are highly O-glycosylated molecules which in mammalian cells ac complish essential functions, like cytoprotection and cell-cell intera ctions. In the protozoan parasite Trypanosoma cruzi, mucin-related gly coproteins have been shown to play a relevant role in the interaction with and invasion of host cells, We have previously reported a family of mucin-like genes in T. cruzi whose overall structure resembled that of mammalian mucin genes, We have now analyzed the relationship betwe en these genes and mucin proteins, a monoclonal antibody specific for a mucin sugar epitope and a polyclonal serum directed to peptide epito pes in a MUC gene-encoded recombinant protein, detected identical band s in three out of seven strains of T, cruzi. Immunoprecipitation exper iments confirmed these results, When expressed in eukaryotic cells, th e MUC gene product is post-translationally modified, most likely, thro ugh extensive O-glycosylation, Gene sequencing showed that the central domains encoding the repeated sequences with the consensus T8KP2, var ies in number from 1 to 10, and the number of Thr residues in each rep eat could be 7, 8, or 10. A run of 16 to 18 Thr residues was present i n some, but not all, MUC gene-derived sequences, Direct compositional analysis of mucin core proteins showed that Thr residues are much more frequent than Ser residues, The same fact occurs in MUC gene-derived protein sequences. Molecular mass determinations of the 35-kDa glycopr oteins further extend the heterogeneity of the family to the natural m ucin molecules. Difficulties in assigning each of the several MUC gene s identified to a mucin product arise from the high diversity and part ial sequence conservation of the members of this family.