The exocytosis-regulatory protein synaptotagminVII mediates cell invasion by Trypanosoma cruzi

The intracellular protozoan parasite Trypanosoma cruzi causes Chagas' disea se, which affects millions of people in Latin America. T. cruzi enters a la rge number of cell types by an unusual mechanism that involves Ca2+-trigger ed fusion of lysosomes with the plasma membrane. Here we show that synaptot agmin VII (Syt VII), a ubiquitously expressed synaptotagmin isoform that re gulates exocytosis of lysosomes, is localised on the membranes of intracell ular vacuoles containing T. cruzi. Antibodies against the C(2)A domain of S yt 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 eff ect 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 ex ploits the Syt VII-dependent, Ca2+-regulated lysosomal exocytic pathway for invading host cells.