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Blood, 15 February 2008, Vol. 111, No. 4, pp. 2418-2426.
Prepublished online as a Blood First Edition Paper on December 5, 2007; DOI 10.1182/blood-2007-09-115279.
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Submitted September 28, 2007
Accepted December 3, 2007
Maurer's clefts of P. falciparum are secretory organelles that concentrate virulence protein reporters for delivery to the host erythrocyte
Souvik Bhattacharjee, Christiaan van Ooij, Bharath Balu, John H Adams, and Kasturi Haldar*
Departments of Pathology and Microbiology-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN, United States
* Corresponding author; email: k-haldar{at}northwestern.edu.
In blood stage infection by the human malaria parasite Plasmodium falciparum, export of proteins from the intracellular parasite to the erythrocyte is key to virulence. This export is mediated by a host-targeting (HT) signal present on a 'secretome' of hundreds of parasite proteins engaged in remodeling the erythrocyte. But the route of HT-mediated export is poorly understood. Here we show that minimal soluble and membrane protein reporters that contain the HT motif and mimic export of endogenous P. falciparum proteins are detected in the lumen of 'cleft' structures synthesized by the pathogen. Clefts are efficiently targeted by the HT signal. Further the HT signal does not directly translocate across the parasitophorous vacuolar membrane (PVM) surrounding the parasite to deliver protein to the erythrocyte cytoplasm, as suggested by current models of parasite protein trafficking to the erythrocyte. Rather, it is a lumenal signal that sorts protein into clefts, which then are exported beyond the PVM. These data suggest that Maurer's clefts, which are unique to the virulent P. falciparum species, are pathogen-induced secretory organelles that concentrate HT-containing soluble and membrane parasite proteins in their lumen for delivery to the host erythrocyte.
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