Article
- The EMBO Journal (2001) 20, 5636 - 5649
- doi:10.1093/emboj/20.20.5636
Trafficking and assembly of the cytoadherence complex in Plasmodium falciparum-infected human erythrocytes
Mark E. Wickham1, Melanie Rug2, Stuart A. Ralph3, Nectarios Klonis2, Geoffrey I. McFadden3, Leann Tilley2 and Alan F. Cowman1
- The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Melbourne 3050, Australia
- Department of Biochemistry, La Trobe University, Melbourne, Australia
- Plant Cell Biology Research Centre, School of Botany, University of Melbourne, Melbourne, Australia
Correspondence to:
Alan F. Cowman, E-mail: cowman@wehi.edu.au
Received 24 July 2001; Accepted 23 August 2001; Revised 22 August 2001
Abstract
After invading human erythrocytes, the malarial parasite Plasmodium falciparum, initiates a remarkable process of secreting proteins into the surrounding erythrocyte cytoplasm and plasma membrane. One of these exported proteins, the knob-associated histidine-rich protein (KAHRP), is essential for microvascular sequestration, a strategy whereby infected red cells adhere via knob structures to capillary walls and thus avoid being eliminated by the spleen. This cytoadherence is an important factor in many of the deaths caused by malaria. Green fluorescent protein fusions and fluorescence recovery after photobleaching were used to follow the pathway of KAHRP deployment from the parasite endomembrane system into an intermediate depot between parasite and host, then onwards to the erythrocyte cytoplasm and eventually into knobs. Sequence elements essential to individual steps in the pathway are defined and we show that parasite-derived structures, known as Maurer's clefts, are an elaboration of the canonical secretory pathway that is transposed outside the parasite into the host cell, the first example of its kind in eukaryotic biology.
Keywords:
- fluorescence recovery after photobleaching,
- green fluorescent protein,
- KAHRP,
- malaria,
- protein trafficking
