HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 34, 24961-24969, August 24, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/34/24961    most recent M703316200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Subramanian, S. Articles by Rosenthal, P. J. Search for Related Content PubMed PubMed Citation Articles by Subramanian, S. Articles by Rosenthal, P. J. Social Bookmarking                      What's this?

Falcipain Cysteine Proteases Require Bipartite Motifs for Trafficking to the Plasmodium falciparum Food Vacuole^*

From the Department of Medicine, Division of Infectious Disease, University of California, San Francisco, San Francisco, California 94143

The Plasmodium falciparum cysteine proteases falcipain-2 and falcipain-3 hydrolyze hemoglobin in an acidic food vacuole to provide amino acids for erythrocytic malaria parasites. Trafficking to the food vacuole has not been well characterized. To study trafficking of falcipains, which include large membrane-spanning prodomains, we utilized chimeras with portions of the proteases fused to green fluorescent protein. The prodomains of falcipain-2 and falcipain-3 were sufficient to target green fluorescent protein to the food vacuole. Using serial truncations, deletions, and point mutations, we showed that both a 20-amino acid stretch of the lumenal portion and a 10-amino acid stretch of the cytoplasmic portion of the falcipain-2 prodomain were required for efficient food vacuolar trafficking. Mutants with altered trafficking were arrested at the plasma membrane, implicating trafficking via this structure. Our results indicate that falcipains utilize a previously undescribed bipartite motif-dependent mechanism for targeting to a hydrolytic organelle, suggesting inhibition of this unique mechanism as a new means of antimalarial chemotherapy.

Received for publication, April 20, 2007 , and in revised form, June 8, 2007.

^* This work was supported by National Institutes of Health Grants AI35800 and AI35707 and a grant from the Medicines for Malaria Venture. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1–S4 and supplemental Table S1.

¹ Both authors contributed equally to this work.

² A Doris Duke Charitable Foundation Distinguished Clinical Scientist. To whom correspondence should be addressed. E-mail: prosenthal{at}medsfgh.ucsf.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. E. Drew, R. Banerjee, E. W. Uffman, S. Gilbertson, P. J. Rosenthal, and D. E. Goldberg Plasmodium Food Vacuole Plasmepsins Are Activated by Falcipains J. Biol. Chem., May 9, 2008; 283(19): 12870 - 12876. [Abstract] [Full Text] [PDF]