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

J. Biol. Chem., Vol. 281, Issue 41, 30745-30754, October 13, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/41/30745    most recent M606523200v1 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 Starnes, G. L. Articles by Sibley, L. D. Search for Related Content PubMed PubMed Citation Articles by Starnes, G. L. Articles by Sibley, L. D. Social Bookmarking                      What's this?

Two Separate, Conserved Acidic Amino Acid Domains within the Toxoplasma gondii MIC2 Cytoplasmic Tail Are Required for Parasite Survival^*

G. Lucas Starnes¹, Travis J. Jewett², Vern B. Carruthers, and L. David Sibley³

From the Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63130-1093 and the Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0620

Apicomplexan parasites rely on actin-based motility to drive host cell invasion. Motility and invasion also require thrombospondin-related anonymous protein (TRAP) adhesins, which are secreted apically and translocated to the posterior end of the parasite before they are shed by the activity of a rhomboid protease. TRAP orthologs, including Toxoplasma gondii MIC2 (microneme protein 2), possess a short cytoplasmic tail, which is essential for motility. Previous studies have shown that aldolase forms a critical bridge between actin filaments and the cytoplasmic domains of MIC2 and TRAP. The cytoplasmic tails of TRAP family members harbor a conserved penultimate tryptophan, which is essential for aldolase binding, and clustered acidic residues. Herein, we determined the role of the conserved acidic residues by using alanine point mutants to investigate aldolase binding in vitro and to test functionality in the parasite. Our studies revealed two separate acidic residue clusters in the cytoplasmic domain of MIC2 that are essential for parasite survival. One region, located at the extreme C terminus, is required for the direct interaction with aldolase, whereas the second upstream acidic region is not necessary for aldolase binding but is nonetheless essential to parasite survival. Both acidic domains are conserved throughout TRAP orthologs, implicating a central role for these motifs in apicomplexan motility.

Received for publication, July 10, 2006 , and in revised form, August 18, 2006.

^* This work was supported in part by National Institutes of Health Grant AI034036 (to L. D. S.). 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.

¹ Supported in part by National Institutes of Health Institutional Training Grant AI017172 (to Washington University).

² Present address: Rocky Mountain National Laboratories, National Institutes of Health, Hamilton, MT 59840.

³ To whom correspondence should be addressed: Dept. of Molecular Microbiology, Washington University School Medicine, P. O. Box 8230, 660 S. Euclid Ave., St. Louis, MO 63130-1093. Tel.: 314-362-8873; Fax: 314-362-1232; E-mail: sibley{at}borcim.wustl.edu.

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

This article has been cited by other articles:

				H. Kessler, A. Herm-Gotz, S. Hegge, M. Rauch, D. Soldati-Favre, F. Frischknecht, and M. Meissner Microneme protein 8 - a new essential invasion factor in Toxoplasma gondii J. Cell Sci., April 1, 2008; 121(7): 947 - 956. [Abstract] [Full Text] [PDF]