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The Trypanosoma cruzi Mucin Coat: Structure, Regulation of the Expression and Relevance in the Host-Parasite Relationship

This chapter appears in the following book:

Molecular Mechanisms of Pathogenesis in Chagas Disease

Edited by: JohnM. Kelly
ISBN: 0-306-47849-8
» Get more information about this book at landesbioscience.com «

Chapter authors:
Javier M. Di Noia, Ivan D'Orso and Alberto Carlos C. Frasch

The cell surface of Trypanosoma cruzi, the agent of the Chagas disease, is covered by a family of highly O-glycosylated mucin-like glycoproteins. This coat protects the parasite from the immune response of the host and is involved in the invasion of mammalian cells. Two major heterogeneous groups have been identified within the mucin family; the 35-50kDa group which is expressed in the parasite stages associated with the insect vector, and the 60-200kDa group which is expressed in the stages present in the vertebrate host. The carbohydrate moieties of the parasite mucins display some differences when compared with those expressed by mammalian cells. The first monosaccharide attached to the protein core is N-acetylglucosamine instead of N-acetylgalactosamine. Furthermore, sialic acid is attached to the oligosaccharide side chains by a unique trans-sialidase activity on the external surface of the parasite, and not in the Golgi apparatus as in most eukaryotic cells. An unexpectedly large number of parasite mucins have now been found after analysis of the genes encoding the core proteins. Two large gene families were identified. The TcSMUG gene family has about 70-80 members and encode the mucins that are expressed during the insect stage of the life-cycle. The second family, TcMUC, is composed of about 500-700 members and includes the genes that are expressed in the vertebrate host. Unlike the mucins expressed in the insect stages, those expressed in the vertebrate stages are characterised by the presence of a hypervariable N-terminal region. This is proposed to have a role in immunoevasion. The formidable task of regulating stage-specific gene expression of these large genes families is achieved, at least in part, through regulation of mRNA stability. Regulatory cis-acting sequences in mucin transcripts and the trans-acting protein factors that bind to these elements have now been identified. Thus, T. cruzi make use of about 1% of its genome and has a complex post-transcriptional regulatory mechanism to generate the mucin coat required for its survival.

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