Structural features affecting trafficking, processing, and secretion of Trypanosoma cruzi mucins

Gaspar E. Cánepa, Andrea C. Mesías, Hai Yu, Xi Chen, Carlos A. Buscaglia

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Trypanosoma cruzi is wrapped by a dense coat of mucin-type molecules encoded by complex gene families termedTcSMUG and TcMUC, which are expressed in the insect- and mammal-dwelling forms of the parasite, respectively. Here, we dissect the contribution of distinct post-translational modifications on the trafficking of these glycoconjugates. In vivo tracing and characterization of tagged-variants expressed by transfected epimastigotes indicate that although the N-terminal signal peptide is responsible for targeting TcSMUG products to the endoplasmic reticulum (ER), the glycosyl phosphatidylinositol (GPI)-anchor likely functions as a forward transport signal for their timely progression along the secretory pathway. GPI-minus variants accumulate in the ER, with only a minor fraction being ultimately released to the medium as anchorless products. Secreted products, but not ER-accumulated ones, display several diagnostic features of mature mucin-type molecules including extensive O-type glycosylation, Galf-based epitopes recognized by monoclonal antibodies, and terminal Galp residues that become readily sialylated upon addition of parasite trans-sialidases. Processing of N-glycosylation site(s) is dispensable for the overall TcSMUG mucin-type maturation and secretion. Despite undergoing different O-glycosylation elaboration, TcMUC reporters yielded quite similar results, thus indicating that (i) molecular trafficking signals are structurally and functionally conserved between mucin families, and (ii) TcMUC and TcSMUG products are recognized and processed by a distinct repertoire of stage-specific glycosyltransferases. Thus, using the fidelity of a homologous expression system, we have defined some biosynthetic aspects of T. cruzi mucins, key molecules involved in parasite protection and virulence.

Original languageEnglish (US)
Pages (from-to)26365-26376
Number of pages12
JournalJournal of Biological Chemistry
Volume287
Issue number31
DOIs
StatePublished - Jul 27 2012

Fingerprint

Trypanosoma cruzi
Mucins
Glycosylation
Endoplasmic Reticulum
Processing
Glycosylphosphatidylinositols
Parasites
Molecules
Glycosyltransferases
Glycoconjugates
Mammals
Secretory Pathway
Post Translational Protein Processing
Protein Sorting Signals
Anchors
Virulence
Insects
Epitopes
Genes
Monoclonal Antibodies

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Structural features affecting trafficking, processing, and secretion of Trypanosoma cruzi mucins. / Cánepa, Gaspar E.; Mesías, Andrea C.; Yu, Hai; Chen, Xi; Buscaglia, Carlos A.

In: Journal of Biological Chemistry, Vol. 287, No. 31, 27.07.2012, p. 26365-26376.

Research output: Contribution to journalArticle

Cánepa, Gaspar E. ; Mesías, Andrea C. ; Yu, Hai ; Chen, Xi ; Buscaglia, Carlos A. / Structural features affecting trafficking, processing, and secretion of Trypanosoma cruzi mucins. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 31. pp. 26365-26376.
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