The Transmembrane Isoform of Plasmodium falciparum MAEBL Is Essential for the Invasion of Anopheles Salivary Glands

Saénz, Fabián E.; Balu, Bharath; Smith, Jonah; Mendonca, Sarita R.; Adams, John

doi:10.1371/journal.pone.0002287

Cited by 45 publications

(56 citation statements)

References 33 publications

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“…Evolutionary developmental biology (evo/devo) uses interspecific transgenic approaches, and advanced transgenic technologies in mosquitoes will increase the opportunities to use these insects in evo/devo studies (34). Virology and parasitology studies investigating virus and parasite biology in mosquitoes also will benefit from advanced transgenic technologies in these insects (35,36). Finally, applied entomology programs focused on the genetic control of mosquito populations or their pathogen transmission characteristics will benefit from the advanced transgenic technologies based on transposon remobilization (37).…”

Section: Discussionmentioning

confidence: 99%

piggyBac transposon remobilization and enhancer detection in Anopheles mosquitoes

O’Brochta

Alford²,

Pilitt³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Technical advances in mosquito biology are enabling the development of new approaches to vector control. Absent are powerful forward-genetics technologies, such as enhancer and gene traps, that permit determination of gene functions from the phenotypes arising from transposon insertion mutations. We show that the piggyBac transposon is highly active in the germline of the human malaria vector Anopheles stephensi. Up to 6% of the progeny from transgenic A. stephensi containing a single 6-kb piggyBac element with a marker gene expressing EGFP had the vector in new genomic locations when piggyBac transposase was provided in trans from a second integrated transgene. The active transposition of piggyBac resulted in the efficient detection of enhancers, with ∼10% of the progeny with piggyBac in new locations with novel patterns of EGFP expression in third and fourth instar larvae and in adults. The availability of advanced transgenic capabilities such as efficient transposon-based forward-genetics technologies for Anopheles mosquitoes not only will accelerate our understanding of mosquito functional genomics and the development of novel vector and disease transmission control strategies, but also will enable studies by evolutionary developmental biologists, virologists, and parasitologists.transposable element | Plasmodium | Drosophila

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Section: Discussionmentioning

confidence: 99%

piggyBac transposon remobilization and enhancer detection in Anopheles mosquitoes

O’Brochta

Alford²,

Pilitt³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…To investigate the functional implications of the AMA4-RON2 L1 complex in T. gondii, we first established that TgAMA4 is part of a highly divergent AMA clade that includes the functionally important malaria vaccine candidate Plasmodium merozoite apical erythrocyte-binding ligand (MAEBL) (18)(19)(20) and that TgRON2 L1 displays a similar divergence consistent with coevolution of receptor and ligand. We then show that TgAMA4 and TgRON2 L1 form a high-affinity binary complex and probe its overall architecture and underlying mechanism of assembly using crystal structures of TgAMA4 in the apo and TgRON2 L1 D3 bound forms.…”

Section: Significancementioning

confidence: 99%

Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMA–RON2 pair

Parker

Penarete-Vargas

Hamilton

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Plasmodium falciparum and Toxoplasma gondii are widely studied parasites in phylum Apicomplexa and the etiological agents of severe human malaria and toxoplasmosis, respectively. These intracellular pathogens have evolved a sophisticated invasion strategy that relies on delivery of proteins into the host cell, where parasite-derived rhoptry neck protein 2 (RON2) family members localize to the host outer membrane and serve as ligands for apical membrane antigen (AMA) family surface proteins displayed on the parasite. Recently, we showed that T. gondii harbors a novel AMA designated as TgAMA4 that shows extreme sequence divergence from all characterized AMA family members. Here we show that sporozoite-expressed TgAMA4 clusters in a distinct phylogenetic clade with Plasmodium merozoite apical erythrocyte-binding ligand (MAEBL) proteins and forms a high-affinity, functional complex with its coevolved partner, TgRON2 L1 . High-resolution crystal structures of TgAMA4 in the apo and TgRON2 L1 -bound forms complemented with alanine scanning mutagenesis data reveal an unexpected architecture and assembly mechanism relative to previously characterized AMA-RON2 complexes. Principally, TgAMA4 lacks both a deep surface groove and a key surface loop that have been established to govern RON2 ligand binding selectivity in other AMAs. Our study reveals a previously underappreciated level of molecular diversity at the parasite-host-cell interface and offers intriguing insight into the adaptation strategies underlying sporozoite invasion. Moreover, our data offer the potential for improved design of neutralizing therapeutics targeting a broad range of AMA-RON2 pairs and apicomplexan invasive stages.Apicomplexa | Toxoplasma gondii | invasion | moving junction | X-ray crystallography P hylum Apicomplexa comprises >5,000 parasitic protozoan species, many of which cause devastating diseases on a global scale. Two of the most prevalent species are Toxoplasma gondii and Plasmodium falciparum, the causative agents of toxoplasmosis and severe human malaria, respectively (1, 2). The obligate intracellular apicomplexan parasites lead complex and diverse lifestyles that require invasion of many different cell types. Despite this diversity of target host cells, most apicomplexans maintain a generally conserved mechanism for active invasion (3). The parasite initially glides over the surface of a host cell and then reorients to place its apical end in close contact to the hostcell membrane. After this initial attachment, a circumferential ring of adhesion (termed the moving or tight junction) is formed, through which the parasite actively propels itself while concurrently depressing the host-cell membrane to create a nascent protective vacuole (4).Formation of the moving junction relies on a pair of highly conserved parasite proteins: rhoptry neck protein 2 (RON2) and apical membrane antigen 1 (AMA1). Initially, parasites discharge RON2 into the host cell membrane where an extracellular portion (domain 3; D3) serves as a ligand for AMA1 displa...

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“…MAEBL is essential for the development of the parasite during sporozoite infection of mosquito salivary glands (26,27) and is also expressed in the salivary gland sporozoite and during the late liver stage (28). Weak expression of MAEBL can also be detected in blood-stage merozoite forms, although maebl deletion has no impact on blood-stage parasite development (26).…”

mentioning

confidence: 99%

Immunization with the MAEBL M2 Domain Protects against Lethal Plasmodium yoelii Infection

et al. 2015

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The Transmembrane Isoform of Plasmodium falciparum MAEBL Is Essential for the Invasion of Anopheles Salivary Glands

Cited by 45 publications

References 33 publications

piggyBac transposon remobilization and enhancer detection in Anopheles mosquitoes

piggyBac transposon remobilization and enhancer detection in Anopheles mosquitoes

Dissecting the interface between apicomplexan parasite and host cell: Insights from a divergent AMA–RON2 pair

Immunization with the MAEBL M2 Domain Protects against Lethal Plasmodium yoelii Infection

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