Spatial organization of protein export in malaria parasite blood stages |
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| Authors: | Sarah C Charnaud Thorey K Jonsdottir Paul R Sanders Hayley E Bullen Benjamin K Dickerman Betty Kouskousis Catherine S Palmer Halina M Pietrzak Annamarie E Laumaea Anna‐Belen Erazo Emma McHugh Leann Tilley Brendan S Crabb Paul R Gilson |
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| Affiliation: | 1. Burnet Institute, Melbourne, Australia;2. Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia;3. Monash Micro Imaging, Monash University, Melbourne, Australia;4. Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Australia;5. Department of Microbiology, Monash University, Melbourne, Australia |
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| Abstract: | Plasmodium falciparum, which causes malaria, extensively remodels its human host cells, particularly erythrocytes. Remodelling is essential for parasite survival by helping to avoid host immunity and assisting in the uptake of plasma nutrients to fuel rapid growth. Host cell renovation is carried out by hundreds of parasite effector proteins that are exported into the erythrocyte across an enveloping parasitophorous vacuole membrane (PVM). The Plasmodium translocon for exported (PTEX) proteins is thought to span the PVM and provide a channel that unfolds and extrudes proteins across the PVM into the erythrocyte. We show that exported reporter proteins containing mouse dihydrofolate reductase domains that inducibly resist unfolding become trapped at the parasite surface partly colocalizing with PTEX. When cargo is trapped, loop‐like extensions appear at the PVM containing both trapped cargo and PTEX protein EXP2, but not additional components HSP101 and PTEX150. Following removal of the block‐inducing compound, export of reporter proteins only partly recovers possibly because much of the trapped cargo is spatially segregated in the loop regions away from PTEX. This suggests that parasites have the means to isolate unfoldable cargo proteins from PTEX‐containing export zones to avert disruption of protein export that would reduce parasite growth.  |
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| Keywords: | erythrocyte luciferase malaria PEXEL
Plasmodium falciparum protein export protein trafficking PTEX translocon |
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