The Exocytosis-regulatory protein synaptotagmin VII mediates cell invasion by Trypanosoma cruzi

The Journal of Experimental Medicine
E V CalerN W Andrews

Abstract

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 Ca(2+)-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 C(2)A 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 C(2)A domains of other ubiquitously expressed synaptotagmin isoforms have no effect on T. cruzi invasion, and mutation of critical residues on Syt VII C(2)A abolish its inhibitory activity. These findings indicate that T. cruzi exploits the Syt VII-dependent, Ca(2+)-regulated lysosomal exocytic pathway for invading host cells.

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Citations

Apr 7, 2005·Molecular and Biochemical Parasitology·Sabyasachi ChakrabartiNorma W Andrews
Jun 19, 2002·Trends in Biochemical Sciences·Richard A KahnCraig R Roy
Jun 2, 2005·Nature Reviews. Molecular Cell Biology·Paul L McNeil, Tom Kirchhausen
Sep 22, 2005·Nature Reviews. Microbiology·Luciana O Andrade, Norma W Andrews
May 5, 2005·Science's STKE : Signal Transduction Knowledge Environment·Norma W Andrews
Sep 24, 2004·Infection and Immunity·Isabela M AparicioAna Paula C A Lima
Oct 23, 2003·Annual Review of Cell and Developmental Biology·Paul L McNeil, Richard A Steinhardt
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Mar 30, 2005·Proceedings of the National Academy of Sciences of the United States of America·Anders HåkanssonMichael R Wessels
Nov 3, 2010·The Journal of Cell Biology·Andrew R FlanneryNorma W Andrews
Sep 20, 2006·The Journal of Cell Biology·Cecilia CzibenerNorma W Andrews
Aug 20, 2003·The Journal of Cell Biology·Sabyasachi ChakrabartiNorma W Andrews
Jul 31, 2002·The Journal of Cell Biology·Norma W Andrews
May 20, 2015·Current Opinion in Microbiology·Guillermo Arango Duque, Albert Descoteaux
Oct 7, 2005·Cellular Microbiology·Kevin M TylerDavid M Engman
Jul 7, 2005·Traffic·Céline CougouleIsabelle Maridonneau-Parini
Feb 17, 2006·Biology of the Cell·Virginie Braun, Florence Niedergang
Mar 29, 2012·IUBMB Life·Patricia Silvia RomanoMaría Isabel Colombo
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Jun 1, 2012·Cellular Microbiology·Claire E Butler, Kevin M Tyler
Sep 20, 2005·Trends in Cell Biology·Norma W Andrews, Sabyasachi Chakrabarti
Jan 12, 2011·Biochemical Pharmacology·Annette DraegerEduard B Babiychuk
Feb 22, 2012·FEMS Microbiology Reviews·Maria Cecilia Fernandes, Norma W Andrews
Jun 20, 2015·BioMed Research International·Carlos Gustavo Vieira de MoraisPatrícia Maria Lourenço Dutra
Jul 6, 2010·Experimental Parasitology·Conrad L EptingDavid M Engman
Sep 24, 2009·Memórias do Instituto Oswaldo Cruz·Maria Julia Manso Alves, Renato Arruda Mortara
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Mar 3, 2004·The Journal of Biological Chemistry·Swathi K RaoNorma W Andrews
Jul 27, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Guillermo Arango DuqueAlbert Descoteaux
Jan 24, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kimberly T FowlerJames W Huleatt
Jul 28, 2018·Cellular and Molecular Life Sciences : CMLS·Adam Horn, Jyoti K Jaiswal
Jan 13, 2021·Cell and Tissue Research·Catherine Meyer-Schwesinger
Jul 3, 2021·Life·Oscar Hernán Rodríguez-BejaranoManuel Alfonso Patarroyo

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Methods Mentioned

BETA
Transfections
PCR
transfection
fluorescence microscopy

Software Mentioned

Metamorph

Related Concepts