The intracellular protozoan parasite Trypanosoma cruzi causes Chagas' disease, which affects millions of people in Latin America. T. cruzi enters a large number of cell types by an unusual mechanism that involves Ca2+-triggered fusion of lysosomes with the plasma membrane. Here we show that synaptotagmin VII (Syt VII), a ubiquitously expressed synaptotagmin isoform that regulates exocytosis of lysosomes, is localized on the membranes of intracellular vacuoles containing T. cruzi. Antibodies against the C2A domain of Syt VII or recombinant peptides including this domain inhibit cell entry by T. cruzi, but not by Toxoplasma gondii or Salmonella typhimurium. The C2A domains of other ubiquitously expressed synaptotagmin isoforms have no effect on T. cruzi invasion, and mutation of critical residues on Syt VII C2A abolish its inhibitory activity. These findings indicate that T. cruzi exploits the Syt VII–dependent, Ca2+-regulated lysosomal exocytic pathway for invading host cells.
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7 May 2001
Brief Definitive Report|
May 07 2001
The Exocytosis-Regulatory Protein Synaptotagmin VII Mediates Cell Invasion by Trypanosoma cruzi
Elisabet V. Caler,
Elisabet V. Caler
aSection of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06520
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Sabyasachi Chakrabarti,
Sabyasachi Chakrabarti
aSection of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06520
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Kimberly T. Fowler,
Kimberly T. Fowler
aSection of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06520
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Swathi Rao,
Swathi Rao
aSection of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06520
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Norma W. Andrews
Norma W. Andrews
aSection of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06520
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Elisabet V. Caler
aSection of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06520
Sabyasachi Chakrabarti
aSection of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06520
Kimberly T. Fowler
aSection of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06520
Swathi Rao
aSection of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06520
Norma W. Andrews
aSection of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06520
Received:
December 22 2000
Revision Requested:
March 13 2001
Accepted:
March 21 2001
Online ISSN: 1540-9538
Print ISSN: 0022-1007
© 2001 The Rockefeller University Press
2001
The Rockefeller University Press
J Exp Med (2001) 193 (9): 1097–1104.
Article history
Received:
December 22 2000
Revision Requested:
March 13 2001
Accepted:
March 21 2001
Citation
Elisabet V. Caler, Sabyasachi Chakrabarti, Kimberly T. Fowler, Swathi Rao, Norma W. Andrews; The Exocytosis-Regulatory Protein Synaptotagmin VII Mediates Cell Invasion by Trypanosoma cruzi. J Exp Med 7 May 2001; 193 (9): 1097–1104. doi: https://doi.org/10.1084/jem.193.9.1097
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