The Journal of Experimental Medicine
Keystone Symposia
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Journal of Experimental Medicine, Vol 184, 1909-1918, Copyright © 1996 by Rockefeller University Press

ARTICLES

Proteasome activity is required for the stage-specific transformation of a protozoan parasite

J Gonzalez, FJ Ramalho-Pinto, U Frevert, J Ghiso, S Tomlinson, J Scharfstein, EJ Corey and V Nussenzweig
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.

A prominent feature of the life cycle of intracellular parasites is the profound morphological changes they undergo during development in the vertebrate and invertebrate hosts. In eukaryotic cells, most cytoplasmic proteins are degraded in proteasomes. Here, we show that the transformation in axenic medium of trypomastigotes of Trypanosoma cruzi into amastigote-like organisms, and the intracellular development of the parasite from amastigotes into trypomastigotes, are prevented by lactacystin, or by a peptide aldehyde that inhibits proteasome function. Clasto-lactacystin, an inactive analogue of lactacystin, and cell-permeant peptide aldehyde inhibitors of T. cruzi cysteine proteinases have no effect. We have also identified the 20S proteasomes from T. cruzi as a target of lactacystin in vivo. Our results document the essential role of proteasomes in the stage-specific transformation of a protozoan.
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