title: Plasmodium knowlesi Skeleton-Binding Protein 1 Localizes to the 'Sinton and Mulligan' Stipplings in the Cytoplasm of Monkey and Human Erythrocytes.
abstract: The malaria parasite, Plasmodium, exports protein products to the infected erythrocyte to introduce modifications necessary for the establishment of nutrient acquisition and surface display of host interaction ligands. Erythrocyte remodeling impacts parasite virulence and disease pathology and is well documented for the human malaria parasite Plasmodium falciparum, but has been less described for other Plasmodium species. For P. falciparum, the exported protein skeleton-binding protein 1 (PfSBP1) is involved in the trafficking of erythrocyte surface ligands and localized to membranous structures within the infected erythrocyte, termed Maurer's clefts. In this study, we analyzed SBP1 orthologs across the Plasmodium genus by BLAST analysis and conserved gene synteny, which were also recently described by de Niz et al. (2016). To evaluate the localization of an SBP1 ortholog, we utilized the zoonotic malaria parasite, Plasmodium knowlesi. Immunofluorescence assay of transgenic P. knowlesi parasites expressing epitope-tagged recombinant PkSBP1 revealed a punctate staining pattern reminiscent of Maurer's clefts, following infection of either monkey or human erythrocytes. The recombinant PkSBP1-positive puncta co-localized with Giemsa-stained structures, known as 'Sinton and Mulligan' stipplings. Immunoelectron microscopy also showed that recombinant PkSBP1 localizes within or on the membranous structures akin to the Maurer's clefts. The recombinant PkSBP1 expressed in P. falciparum-infected erythrocytes co-localized with PfSBP1 at the Maurer's clefts, indicating an analogous trafficking pattern. A member of the P. knowlesi 2TM protein family was also expressed and localized to membranous structures in infected monkey erythrocytes. These results suggest that the trafficking machinery and induced erythrocyte cellular structures of P. knowlesi are similar following infection of both monkey and human erythrocytes, and are conserved with P. falciparum.
authors.affiliation: Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Sakamoto, Nagasaki 852-8523, Japan.|Leading program, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Amuza Byaruhanga
authors.initials: AB
authors.lastname: Lucky
authors.affiliation: Central Laboratory, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Miako
authors.initials: M
authors.lastname: Sakaguchi
authors.affiliation: The Corporation for Production and Research of Laboratory Primates, Tsukuba 305-0843, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Katakai
authors.affiliation: Department of Tropical Medicine and Parasitology, Dokkyo Medical University, Tochigi 321-0293, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawai
authors.affiliation: Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Yahata
authors.affiliation: Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Sakamoto, Nagasaki 852-8523, Japan.|Department of Microbiology and Immunology, Weill Cornell Medical College, New York 10021, United States of America.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Templeton
authors.affiliation: Department of Protozoology, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Sakamoto, Nagasaki 852-8523, Japan.|Leading program, Graduate School of Biomedical Sciences, Nagasaki University, Sakamoto, Nagasaki 852-8523, Japan.
authors.forename: Osamu
authors.identifier: http://orcid.org/0000-0003-0675-8296
authors.initials: O
authors.lastname: Kaneko
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology* / Q000473:pathology*; D000882:Haplorhini; D006801:Humans; D008288:Malaria / Q000378:metabolism / Q000469:parasitology* / Q000473:pathology*; D016790:Plasmodium knowlesi / Q000502:physiology*; D021381:Protein Transport; D015800:Protozoan Proteins / Q000032:analysis / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D015800:Protozoan Proteins; C000619472:SBP1 protein, Plasmodium knowlesi