The Exocytosis-regulatory protein synaptotagmin VII mediates cell invasion by Trypanosoma cruzi.
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.
Caler
E V
EV
Section of Microbial Pathogenesis, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Chakrabarti
S
S
Fowler
K T
KT
Rao
S
S
Andrews
N W
NW
D016475:3T3 Cells; D000818:Animals; D016466:CHO Cells; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D005089:Exocytosis / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D050857:Synaptotagmins; D014349:Trypanosoma cruzi / Q000472:pathogenicity*
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C494302:SYT7 protein, human; C494303:Syt7 protein, mouse; D050857:Synaptotagmins