J. Cell Biol.
© The Rockefeller University Press
0021-9525/97/02/609/12 $2.00
Volume 136, Number 3, February 10, 1997 609-620

A Cytosolic Serine Endopeptidase from Trypanosoma cruzi Is Required for the Generation of Ca²⁺ Signaling in Mammalian Cells

Barbara A. Burleigh, Elisabet V. Caler, Paul Webster, and Norma W. Andrews

Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520-8002

An early event in the Trypanosoma cruzi cell invasion process, the recruitment of host lysosomes, led us to investigate the involvement of signal transduction. Infective trypomastigotes were found to contain a soluble Ca²⁺-signaling activity for mammalian cells that is sensitive to protease inhibitors. Inhibitor and substrate utilization profiles were used to purify a candidate peptidase for involvement in this process, from which we isolated a full-length cDNA clone. The sequence revealed a novel enzyme, denominated T. cruzi oligopeptidase B, which is homologous to members of the prolyl oligopeptidase family of serine hydrolases, known to participate in the maturation of biologically active peptides. The T. cruzi oligopeptidase B was expressed as a fully active product in Escherichia coli, and antibodies to the recombinant enzyme inhibited both peptidase activity and Ca²⁺ signaling induced in normal rat kidney cells by trypomastigote extracts. Our data suggest that the T. cruzi oligopeptidase B participates in processing events in the cytoplasm of the parasites, generating a factor with Ca²⁺-signaling activity for mammalian cells.

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