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Conservation of a gliding motility and cell invasion machinery in Apicomplexan parasites.

Kappe S, Bruderer T, Gantt S, Fujioka H, Nussenzweig V, Ménard R - J. Cell Biol. (1999)

Bottom Line: Most Apicomplexan parasites, including the human pathogens Plasmodium, Toxoplasma, and Cryptosporidium, actively invade host cells and display gliding motility, both actions powered by parasite microfilaments.We also demonstrate that TRAP-related proteins in other Apicomplexa fulfill the same function and that their cytoplasmic tails interact with homologous partners in the respective parasite.Therefore, a mechanism of surface redistribution of TRAP-related proteins driving gliding locomotion and cell invasion is conserved among Apicomplexan parasites.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, USA.

ABSTRACT
Most Apicomplexan parasites, including the human pathogens Plasmodium, Toxoplasma, and Cryptosporidium, actively invade host cells and display gliding motility, both actions powered by parasite microfilaments. In Plasmodium sporozoites, thrombospondin-related anonymous protein (TRAP), a member of a group of Apicomplexan transmembrane proteins that have common adhesion domains, is necessary for gliding motility and infection of the vertebrate host. Here, we provide genetic evidence that TRAP is directly involved in a capping process that drives both sporozoite gliding and cell invasion. We also demonstrate that TRAP-related proteins in other Apicomplexa fulfill the same function and that their cytoplasmic tails interact with homologous partners in the respective parasite. Therefore, a mechanism of surface redistribution of TRAP-related proteins driving gliding locomotion and cell invasion is conserved among Apicomplexan parasites.

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Gliding phenotypes of wild-type and mutant sporozoites. (A) Time-lapse micrographs of sporozoites gliding on uncoated glass slides. Sporozoites were collected from the hemolymph of infected mosquitoes at days 14–16 postfeeding and kept 2 h in 3% BSA at 4°C before microscopic examination. The parasite population and a schematic representation of the TRAP cytoplasmic tail are shown at left. Wild-type, INCO, and TMIC gliding sporozoites described circular patterns and completed one circle in ∼20 s. ACID, TRYP, and TΔS gliding sporozoites described a “pendulum” movement covering one third of a circle and going back to the starting position, repeated several times (shown here with an ACID sporozoite). Numbers indicate seconds. (B) Immunofluorescence using TRAP antirepeat antibodies of trails left behind WT sporozoites gliding over glass slides. Note in the top panels (phase + immunofluorescence at left) the presence of a “ring” of TRAP around the middle portion of the sporozoite. Unlike the glycosylphosphatidylinositol-anchored CS protein of Plasmodium sporozoites that is uniformly deposited in the trail (Stewart and Vanderberg 1988), TRAP found in the trail displays a periodic intensity pattern reminiscent of the nonuniform expression of TRAP on the sporozoite surface (see also Fig. 2 B).
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Figure 3: Gliding phenotypes of wild-type and mutant sporozoites. (A) Time-lapse micrographs of sporozoites gliding on uncoated glass slides. Sporozoites were collected from the hemolymph of infected mosquitoes at days 14–16 postfeeding and kept 2 h in 3% BSA at 4°C before microscopic examination. The parasite population and a schematic representation of the TRAP cytoplasmic tail are shown at left. Wild-type, INCO, and TMIC gliding sporozoites described circular patterns and completed one circle in ∼20 s. ACID, TRYP, and TΔS gliding sporozoites described a “pendulum” movement covering one third of a circle and going back to the starting position, repeated several times (shown here with an ACID sporozoite). Numbers indicate seconds. (B) Immunofluorescence using TRAP antirepeat antibodies of trails left behind WT sporozoites gliding over glass slides. Note in the top panels (phase + immunofluorescence at left) the presence of a “ring” of TRAP around the middle portion of the sporozoite. Unlike the glycosylphosphatidylinositol-anchored CS protein of Plasmodium sporozoites that is uniformly deposited in the trail (Stewart and Vanderberg 1988), TRAP found in the trail displays a periodic intensity pattern reminiscent of the nonuniform expression of TRAP on the sporozoite surface (see also Fig. 2 B).

Mentions: As shown in Table , TMIC sporozoites behaved similarly to WT or INCO sporozoites in all tests performed. Most strikingly, TMIC sporozoites glided at the same average speed and followed a similar circular pattern than WT or INCO sporozoites (Fig. 3 A). In addition, TMIC sporozoites were as infectious to the rodent host as WT sporozoites. In all rodent infection experiments, Southern hybridization indicated that the blood stages of the parasite induced by TMIC sporozoites still contained the TMIC recombinant locus (data not shown), with no trace of WT TRAP that could have been recreated via plasmid excision. We conclude that the cytoplasmic tail of MIC2, despite little primary amino acid sequence similarity to the TRAP cytoplasmic tail, can function in its place during gliding locomotion and cell invasion by malaria sporozoites. The cytoplasmic tails of these proteins must then interact with homologous partners in the respective Apicomplexan host.


Conservation of a gliding motility and cell invasion machinery in Apicomplexan parasites.

Kappe S, Bruderer T, Gantt S, Fujioka H, Nussenzweig V, Ménard R - J. Cell Biol. (1999)

Gliding phenotypes of wild-type and mutant sporozoites. (A) Time-lapse micrographs of sporozoites gliding on uncoated glass slides. Sporozoites were collected from the hemolymph of infected mosquitoes at days 14–16 postfeeding and kept 2 h in 3% BSA at 4°C before microscopic examination. The parasite population and a schematic representation of the TRAP cytoplasmic tail are shown at left. Wild-type, INCO, and TMIC gliding sporozoites described circular patterns and completed one circle in ∼20 s. ACID, TRYP, and TΔS gliding sporozoites described a “pendulum” movement covering one third of a circle and going back to the starting position, repeated several times (shown here with an ACID sporozoite). Numbers indicate seconds. (B) Immunofluorescence using TRAP antirepeat antibodies of trails left behind WT sporozoites gliding over glass slides. Note in the top panels (phase + immunofluorescence at left) the presence of a “ring” of TRAP around the middle portion of the sporozoite. Unlike the glycosylphosphatidylinositol-anchored CS protein of Plasmodium sporozoites that is uniformly deposited in the trail (Stewart and Vanderberg 1988), TRAP found in the trail displays a periodic intensity pattern reminiscent of the nonuniform expression of TRAP on the sporozoite surface (see also Fig. 2 B).
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Related In: Results  -  Collection

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Figure 3: Gliding phenotypes of wild-type and mutant sporozoites. (A) Time-lapse micrographs of sporozoites gliding on uncoated glass slides. Sporozoites were collected from the hemolymph of infected mosquitoes at days 14–16 postfeeding and kept 2 h in 3% BSA at 4°C before microscopic examination. The parasite population and a schematic representation of the TRAP cytoplasmic tail are shown at left. Wild-type, INCO, and TMIC gliding sporozoites described circular patterns and completed one circle in ∼20 s. ACID, TRYP, and TΔS gliding sporozoites described a “pendulum” movement covering one third of a circle and going back to the starting position, repeated several times (shown here with an ACID sporozoite). Numbers indicate seconds. (B) Immunofluorescence using TRAP antirepeat antibodies of trails left behind WT sporozoites gliding over glass slides. Note in the top panels (phase + immunofluorescence at left) the presence of a “ring” of TRAP around the middle portion of the sporozoite. Unlike the glycosylphosphatidylinositol-anchored CS protein of Plasmodium sporozoites that is uniformly deposited in the trail (Stewart and Vanderberg 1988), TRAP found in the trail displays a periodic intensity pattern reminiscent of the nonuniform expression of TRAP on the sporozoite surface (see also Fig. 2 B).
Mentions: As shown in Table , TMIC sporozoites behaved similarly to WT or INCO sporozoites in all tests performed. Most strikingly, TMIC sporozoites glided at the same average speed and followed a similar circular pattern than WT or INCO sporozoites (Fig. 3 A). In addition, TMIC sporozoites were as infectious to the rodent host as WT sporozoites. In all rodent infection experiments, Southern hybridization indicated that the blood stages of the parasite induced by TMIC sporozoites still contained the TMIC recombinant locus (data not shown), with no trace of WT TRAP that could have been recreated via plasmid excision. We conclude that the cytoplasmic tail of MIC2, despite little primary amino acid sequence similarity to the TRAP cytoplasmic tail, can function in its place during gliding locomotion and cell invasion by malaria sporozoites. The cytoplasmic tails of these proteins must then interact with homologous partners in the respective Apicomplexan host.

Bottom Line: Most Apicomplexan parasites, including the human pathogens Plasmodium, Toxoplasma, and Cryptosporidium, actively invade host cells and display gliding motility, both actions powered by parasite microfilaments.We also demonstrate that TRAP-related proteins in other Apicomplexa fulfill the same function and that their cytoplasmic tails interact with homologous partners in the respective parasite.Therefore, a mechanism of surface redistribution of TRAP-related proteins driving gliding locomotion and cell invasion is conserved among Apicomplexan parasites.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Kaplan Cancer Center, New York University School of Medicine, New York, New York 10016, USA.

ABSTRACT
Most Apicomplexan parasites, including the human pathogens Plasmodium, Toxoplasma, and Cryptosporidium, actively invade host cells and display gliding motility, both actions powered by parasite microfilaments. In Plasmodium sporozoites, thrombospondin-related anonymous protein (TRAP), a member of a group of Apicomplexan transmembrane proteins that have common adhesion domains, is necessary for gliding motility and infection of the vertebrate host. Here, we provide genetic evidence that TRAP is directly involved in a capping process that drives both sporozoite gliding and cell invasion. We also demonstrate that TRAP-related proteins in other Apicomplexa fulfill the same function and that their cytoplasmic tails interact with homologous partners in the respective parasite. Therefore, a mechanism of surface redistribution of TRAP-related proteins driving gliding locomotion and cell invasion is conserved among Apicomplexan parasites.

Show MeSH
Related in: MedlinePlus