Document Detail

Identification of glycoproteins targeted by Trypanosoma cruzi trans-sialidase, a virulence factor that disturbs lymphocyte glycosylation.
MedLine Citation:
PMID:  20354005     Owner:  NLM     Status:  MEDLINE    
Trypanosoma cruzi, the agent of the American trypanosomiasis or Chagas disease, bypasses its lack of de novo synthesis of sialic acids by expressing a surface-anchored trans-sialidase. This enzyme transfers sialic acid residues from the host's sialylglycoconjugates to the parasite's galactosylglycoconjugates. In addition to carrying out a pivotal role in parasite persistence/replication within the infected mammal, the trans-sialidase is shed into the bloodstream and induces alterations in the host immune system by modifying the sialylation of the immune cells. A major obstacle to understand these events is the difficulty to identify the transferred sialic acid among all those naturally occurring on the cell surface. Here, we report the use of azido-modified unnatural sialic acid to identify those molecules that act as cell surface acceptors of the sialyl residue in the trans-sialidase-catalyzed reaction, which might then be involved in the immune alterations induced. In living parasites, we readily observed the transfer of azido-sialic acid to surface mucins. When evaluating mouse thymocytes and splenocytes as acceptors of the azido-sugar, a complex pattern of efficiently tagged glycoproteins was revealed. In both leukocyte populations, the main proteins labeled were identified as different CD45 isoforms. Disruption of the cell architecture increased the number and the molecular weight distribution of azido-sialic acid tagged proteins. Nevertheless, CD45 remained to be the main acceptor. Mass spectrometry assays allowed us to identify other acceptors, mainly integrins. The findings reported here provide a molecular basis to understand the abnormalities induced in the immune system by the trans-sialidase during T. cruzi infection.
Romina P Muiá; Hai Yu; Jennifer A Prescher; Ulf Hellman; Xi Chen; Carolyn R Bertozzi; Oscar Campetella
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-03-30
Journal Detail:
Title:  Glycobiology     Volume:  20     ISSN:  1460-2423     ISO Abbreviation:  Glycobiology     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-03     Completed Date:  2010-10-12     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  9104124     Medline TA:  Glycobiology     Country:  England    
Other Details:
Languages:  eng     Pagination:  833-42     Citation Subset:  IM    
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MeSH Terms
Glycoproteins / chemistry*,  metabolism
Host-Parasite Interactions
Jurkat Cells
Lymphocytes / metabolism*
Mass Spectrometry
Mice, Inbred C57BL
Neuraminidase / chemistry*,  metabolism
Protozoan Proteins / chemistry*,  metabolism
Trypanosoma cruzi / enzymology*,  metabolism,  pathogenicity*
Virulence Factors / chemistry*,  metabolism
Grant Support
D43 TW007888-04/TW/FIC NIH HHS; D43TW007888/TW/FIC NIH HHS; R01 AI075589/AI/NIAID NIH HHS; R01 AI075589-02/AI/NIAID NIH HHS; R01 AI075589-03/AI/NIAID NIH HHS; R01 AI075589-04/AI/NIAID NIH HHS; R01AI075589/AI/NIAID NIH HHS
Reg. No./Substance:
0/Glycoproteins; 0/Protozoan Proteins; 0/Virulence Factors; EC 3.2.1.-/trans-sialidase; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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