Targeted mutagenesis of the ring-exported protein-1 of Plasmodium falciparum disrupts the architecture of Maurer's cleft organelles

Hanssen, Eric, Hawthorne, Paula, Dixon, Matthew W. A., Trenholme, Katharine R, McMillan, Paul J., Spielmann, Tobias, Gardiner, Donald L. and Tilley, Leann (2008) Targeted mutagenesis of the ring-exported protein-1 of Plasmodium falciparum disrupts the architecture of Maurer's cleft organelles. Molecular Microbiology, 69 4: 938-953. doi:10.1111/j.1365-2958.2008.06329.x


Author Hanssen, Eric
Hawthorne, Paula
Dixon, Matthew W. A.
Trenholme, Katharine R
McMillan, Paul J.
Spielmann, Tobias
Gardiner, Donald L.
Tilley, Leann
Title Targeted mutagenesis of the ring-exported protein-1 of Plasmodium falciparum disrupts the architecture of Maurer's cleft organelles
Formatted title
Targeted mutagenesis of the ring-exported protein-1 of Plasmodium falciparum disrupts the architecture of Maurer's cleft organelles
Journal name Molecular Microbiology   Check publisher's open access policy
ISSN 0950-382X
Publication date 2008-08
Year available 2008
Sub-type Article (original research)
DOI 10.1111/j.1365-2958.2008.06329.x
Volume 69
Issue 4
Start page 938
End page 953
Total pages 16
Editor T. Pugsley
Place of publication United Kingdom
Publisher Wiley-Blackwell Publishing Ltd.
Collection year 2009
Language eng
Subject C1
9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
110803 Medical Parasitology
Abstract Mature red blood cells have no internal trafficking machinery, so the intraerythrocytic malaria parasite, Plasmodium falciparum, establishes its own transport system to export virulence factors to the red blood cell surface. Maurer's clefts are parasite-derived membranous structures that form an important component of this exported secretory system. A protein with sequence similarity to a Golgi tethering protein, referred to as ring-exported protein-1 (REX1), is associated with Maurer's clefts. A REX1–GFP chimera is trafficked to the Maurer's clefts and preferentially associates with the edges of these structures, as well as with vesicle-like structures and with stalk-like extensions that are involved in tethering the Maurer's clefts to other membranes. We have generated transfected P. falciparum expressing REX1 truncations or deletion. Electron microscopy reveals that the Maurer's clefts of REX1 truncation mutants have stacked cisternae, while the 3D7 parent line has unstacked Maurer's clefts. D10 parasites, which have lost the right end of chromosome 9, including the rex1 gene, also display Maurer's clefts with stacked cisternae. Expression of full-length REX1–GFP in D10 parasites restores the 3D7-type unstacked Maurer's cleft phenotype. These studies reveal the importance of the REX1 protein in determining the ultrastructure of the Maurer's cleft system.
Formatted abstract
Mature red blood cells have no internal trafficking machinery, so the intraerythrocytic malaria parasite, Plasmodium falciparum, establishes its own transport system to export virulence factors to the red blood cell surface. Maurer's clefts are parasite-derived membranous structures that form an important component of this exported secretory system. A protein with sequence similarity to a Golgi tethering protein, referred to as ring-exported protein-1 (REX1), is associated with Maurer's clefts. A REX1–GFP chimera is trafficked to the Maurer's clefts and preferentially associates with the edges of these structures, as well as with vesicle-like structures and with stalk-like extensions that are involved in tethering the Maurer's clefts to other membranes. We have generated transfected P. falciparum expressing REX1 truncations or deletion. Electron microscopy reveals that the Maurer's clefts of REX1 truncation mutants have stacked cisternae, while the 3D7 parent line has unstacked Maurer's clefts. D10 parasites, which have lost the right end of chromosome 9, including the rex1 gene, also display Maurer's clefts with stacked cisternae. Expression of full-length REX1–GFP in D10 parasites restores the 3D7-type unstacked Maurer's cleft phenotype. These studies reveal the importance of the REX1 protein in determining the ultrastructure of the Maurer's cleft system.
Keyword Plasmodium falciparum
Maurer's clefts
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2009 Higher Education Research Data Collection
Excellence in Research Australia (ERA) - Collection
School of Medicine Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 43 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 43 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 06 Apr 2009, 17:00:18 EST by Amanda Jones on behalf of School of Medicine