Variant Exported Blood-Stage Proteins Encoded by Plasmodium Multigene Families Are Expressed in Liver Stages Where They Are Exported into the Parasitophorous Vacuole.

Autor:	Fougère A; Leiden Malaria Research Group, Parasitology, Center of infectious Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands.; Department of Experimental Medicine, University of Perugia, Italy., Jackson AP; Department of Infection Biology, Institute of Infection and Global Health, University of Liverpool, Liverpool, UnitedKingdom., Bechtsi DP; The Francis Crick Institute, Mill Hill Laboratory, Mill Hill, London, UnitedKingdom., Braks JA; Leiden Malaria Research Group, Parasitology, Center of infectious Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Annoura T; Leiden Malaria Research Group, Parasitology, Center of infectious Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands.; Department of Department of Parasitology, National Institute of Infectious Diseases (NIID), Tokyo, Japan., Fonager J; Leiden Malaria Research Group, Parasitology, Center of infectious Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands.; Department of Microbiological Diagnostics and Virology, Statens Serum Institute, Copenhagen, Denmark., Spaccapelo R; Department of Experimental Medicine, University of Perugia, Italy., Ramesar J; Leiden Malaria Research Group, Parasitology, Center of infectious Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Chevalley-Maurel S; Leiden Malaria Research Group, Parasitology, Center of infectious Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Klop O; Leiden Malaria Research Group, Parasitology, Center of infectious Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands.; Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands., van der Laan AM; Department of Molecular Cell Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Tanke HJ; Department of Molecular Cell Biology, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Kocken CH; Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands., Pasini EM; Biomedical Primate Research Centre (BPRC), Rijswijk, The Netherlands., Khan SM; Leiden Malaria Research Group, Parasitology, Center of infectious Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Böhme U; Wellcome Trust Sanger Institute, Hinxton, Cambridge, UnitedKingdom., van Ooij C; The Francis Crick Institute, Mill Hill Laboratory, Mill Hill, London, UnitedKingdom., Otto TD; Wellcome Trust Sanger Institute, Hinxton, Cambridge, UnitedKingdom., Janse CJ; Leiden Malaria Research Group, Parasitology, Center of infectious Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands., Franke-Fayard B; Leiden Malaria Research Group, Parasitology, Center of infectious Diseases, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
Jazyk:	angličtina
Zdroj:	PLoS pathogens [PLoS Pathog] 2016 Nov 16; Vol. 12 (11), pp. e1005917. Date of Electronic Publication: 2016 Nov 16 (Print Publication: 2016).
DOI:	10.1371/journal.ppat.1005917
Abstrakt:	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. Competing Interests: The authors have declared that no competing interests exist.
Databáze:	MEDLINE
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