Variant exported blood-stage proteins encoded by Plasmodium multigene families are expressed in liver stages where they are exported into the parasitophorous vacuole

Fougère, A. et al. (2016) Variant exported blood-stage proteins encoded by Plasmodium multigene families are expressed in liver stages where they are exported into the parasitophorous vacuole. PLoS Pathogens, 12(11), e1005917. (doi: 10.1371/journal.ppat.1005917) (PMID:27851824) (PMCID:PMC5113031)

Abstract

Many variant proteins encoded by Plasmodium-specific multigene families are exported into red blood cells (RBC). P. falciparum-specific variant proteins encoded by the var, stevor and rifin multigene families are exported onto the surface of infected red blood cells (iRBC) and mediate interactions between iRBC and host cells resulting in tissue sequestration and rosetting. However, the precise function of most other Plasmodium multigene families encoding exported proteins is unknown. To understand the role of RBC-exported proteins of rodent malaria parasites (RMP) we analysed the expression and cellular location by fluorescent-tagging of members of the pir, fam-a and fam-b multigene families. Furthermore, we performed phylogenetic analyses of the fam-a and fam-b multigene families, which indicate that both families have a history of functional differentiation unique to RMP. We demonstrate for all three families that expression of family members in iRBC is not mutually exclusive. Most tagged proteins were transported into the iRBC cytoplasm but not onto the iRBC plasma membrane, indicating that they are unlikely to play a direct role in iRBC-host cell interactions. Unexpectedly, most family members are also expressed during the liver stage, where they are transported into the parasitophorous vacuole. This suggests that these protein families promote parasite development in both the liver and blood, either by supporting parasite development within hepatocytes and erythrocytes and/or by manipulating the host immune response. Indeed, in the case of Fam-A, which have a steroidogenic acute regulatory-related lipid transfer (START) domain, we found that several family members can transfer phosphatidylcholine in vitro. These observations indicate that these proteins may transport (host) phosphatidylcholine for membrane synthesis. This is the first demonstration of a biological function of any exported variant protein family of rodent malaria parasites.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Otto, Professor Thomas and Bechtsi, Miss Dafni Paraskevi
• Authors: Fougère, A., Jackson, A. P., Bechtsi, D. P., Braks, J. A. M., Annoura, T., Fonager, J., Spaccapelo, R., Ramesar, J., Chevalley-Maurel, S., Klop, O., van der Laan, A. M. A., Tanke, H. J., Kocken, C. H. M., Pasini, E. M., Khan, S. M., Böhme, U., van Ooij, C., Otto, T. D., Janse, C. J., and Franke-Fayard, B.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: PLoS Pathogens
• Publisher: Public Library of Science
• ISSN: 1553-7366
• ISSN (Online): 1553-7374
• Copyright Holders: Copyright ©2016 The Authors
• First Published: First published in PLoS Pathogens 12(11): e1005917
• Publisher Policy: Reproduced under a Creative Commons License