Genesis of and Trafficking to the Maurer's Clefts of Plasmodium falciparum-Infected Erythrocytes

Abstract

Malaria parasites export proteins beyond their own plasma membrane to locations in the red blood cells in which they reside. Maurer's clefts are parasite-derived structures within the host cell cytoplasm that are thought to function as a sorting compartment between the parasite and the erythrocyte membrane. However, the genesis of this compartment and the signals directing proteins to the Maurer's clefts are not known. We have generated Plasmodium falciparum-infected erythrocytes expressing green fluorescent protein (GFP) chimeras of a Maurer's cleft resident protein, the membrane-associated histidine-rich protein 1 (MAHRP1). Chimeras of full-length MAHRP1 or fragments containing part of the N-terminal domain and the transmembrane domain are successfully delivered to Maurer's clefts. Other fragments remain trapped within the parasite. Fluorescence photobleaching and time-lapse imaging techniques indicate that MAHRP1-GFP is initially trafficked to isolated subdomains in the parasitophorous vacuole membrane that appear to represent nascent Maurer's clefts. The data suggest that the Maurer's clefts bud from the parasitophorous vacuole membrane and diffuse within the erythrocyte cytoplasm before taking up residence at the cell periphery.

Supplemental material for this article may be found at http://mcb.asm.org/.

This work was supported by the National Health and Medical Research Council, Australia, and the Swiss National Science Foundation (grant number 3100A0-104043/1). D.J.P.F. is supported by an equipment grant from the Wellcome Trust.

Expert technical assistance was provided by Emma Fox. We thank Selina Bopp and Christian Flück for constructive discussions and Paula Hawthorne, QIMR, and Mike Ryan, La Trobe University, Australia, for providing antibodies.