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.
Article|
November 01 1996
Proteasome activity is required for the stage-specific transformation of a protozoan parasite.
J González,
J González
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.
Search for other works by this author on:
F J Ramalho-Pinto,
F J Ramalho-Pinto
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.
Search for other works by this author on:
U Frevert,
U Frevert
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.
Search for other works by this author on:
J Ghiso,
J Ghiso
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.
Search for other works by this author on:
S Tomlinson,
S Tomlinson
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.
Search for other works by this author on:
J Scharfstein,
J Scharfstein
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.
Search for other works by this author on:
E J Corey,
E J Corey
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.
Search for other works by this author on:
V Nussenzweig
V Nussenzweig
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.
Search for other works by this author on:
J González
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.
F J Ramalho-Pinto
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.
U Frevert
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.
J Ghiso
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.
S Tomlinson
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.
J Scharfstein
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.
E J Corey
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.
V Nussenzweig
Michael Heidelberger Division of Immunology, Department of Pathology, New York, University Medical Center, New York 10016, USA.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1996) 184 (5): 1909–1918.
Citation
J González, F J Ramalho-Pinto, U Frevert, J Ghiso, S Tomlinson, J Scharfstein, E J Corey, V Nussenzweig; Proteasome activity is required for the stage-specific transformation of a protozoan parasite.. J Exp Med 1 November 1996; 184 (5): 1909–1918. doi: https://doi.org/10.1084/jem.184.5.1909
Download citation file:
