Cerebral malaria is a severe complication of Plasmodium falciparum infection that causes the loss of blood-brain barrier integrity and frequently results in death. Here, we compared the effect of P. falciparum -infected red blood cells and inflammatory cytokines, like TNF-α, in the loss of BBB integrity.
Avian malaria is of significant ecological importance and serves as a model system to study broad patterns of host switching and host-specificity. The erythrocyte invasion mechanism of the malaria parasite Plasmodium is mediated, in large part, by proteins of the erythrocyte binding-like (ebl) family of genes. However, little is known about how these genes are conserved across different species of Plasmodium, especially those that infect birds. Using bioinformatical methods in conjunction with PCR and genetic sequencing, we identified and annotated one member of the ebl family, maebl (merozoite apical erythrocyte binding ligand) from the chicken parasite Plasmodium gallinaceum. We then detected the expression of maebl in P. gallinaceum by PCR analysis of cDNA isolated from the blood of infected chickens. We found that maebl is a conserved orthologous gene in avian, mammalian, and rodent Plasmodium species. The duplicate extracellular binding domains of MAEBL, responsible for erythrocyte binding, are the most conserved regions. Our combined data corroborate the conservation of maebl throughout the Plasmodium genus, and may help elucidate the mechanisms of erythrocyte invasion in P. gallinaceum and the host specificity of Plasmodium parasites.
Deregulation of various cellular pathways such as the immune, mRNA translation and cell cycle pathways have been linked to autism disorders, yet the cause of deregulation remains unclear. Here we study the Cytoplasmic Activation/Proliferation‐Associated Protein‐1 (Caprin1), an RNA binding protein implicated in autism. In neurons, Caprin1 binds and represses the translation of selective mRNAs at RNA granules. Upon various stimulations such as with brain derived neurotropic factor (BDNF), mRNAs dissociate from Caprin1 and shift into actively translating ribosomes. In addition, studies identified Caprin1 as a positive cell cycle regulator, allowing cells to transition between G1 and S phase by binding to upregulated cell cycle mRNAs. Yet, how Caprin1 mediates repression or promotion of different mRNAs is not well understood. To identify and understand the global mechanism of Caprin1 we conducted a series of high throughput assays including mass‐spectrometry‐based quantitative proteomics and RNAseq. We show that in the absence of Caprin1, cell cycle and cell metabolic genes were significantly decreased. On the other hand, absence of Caprin1 significantly increased genes involved in immune responses, including antigen processing. To further identify a mechanism we conducted a crosslinking‐immunoprecipitation (CLIP) assay to identify mRNAs bound directly to Caprin1. We find that Caprin1 mainly binds to mRNAs upstream of cytokine signaling and cell cycle pathways at the 3′UTR. We further show that Caprin1 degrades or stabilizes different bound mRNAs. Thus, we conclude that Caprin1 has a role in RNA stability, particularly in genes involved in cell cycle and immune response pathways, which are deregulated and implicated in autism.Support or Funding InformationRobertson Foundation, NIH R01AI090110 Supplement, Howard Hughes Medical Institute (HHMI)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
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