Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from <i>Necator americanus</i>

Rey-Burusco, M. Florencia; Shimabukuro, Marina Ibáñez; Gabrielsen, Mads; Franchini, Gisela Raquel; Roe, Andrew J.; Griffiths, Kate; Zhan, Bin; Cooper, Alan; Kennedy, Malcolm W.; Córsico, Betina; Smith, Brian O.

doi:10.1042/bj20150068

Cited by 28 publications

(50 citation statements)

References 71 publications

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“…Predictions of the 3D structure of Mj‐FAR‐1 also reveal new features for this protein when compared to the 3D crystal structure of Ce‐FAR‐7, such as a bigger electrostatically charged P2 pocket that could accommodate larger isoprenoid chains of retinol and other compounds with charged characteristics (Iberkleid et al ., ). These differences are in agreement with the 3D structure of the Na‐FAR‐1 of N. americanus determined by nuclear magnetic resonance and X‐ray crystallography, probably reflecting differences in their ligand selectivity (Rey‐Burusco et al ., ). One route to determine the function of FAR‐1 of M. javanica has been recently performed by overexpressing Mj‐far‐1 in stable hairy root lines of tomato, and studying the consequential gene expression changes by transcriptome data analyses (Iberkleid et al ., ).…”

Section: Discussionmentioning

confidence: 97%

“…Nematode lipid-binding proteins play key roles in the transport of fatty acids and retinols, which are ultimately consumed for important metabolic and developmental processes of the nematode, such as embryogenesis, glycoprotein synthesis, growth and cellular differentiation (McDermott et al, 1999;Kennedy, 2000). Fluorescencebased ligand binding assays have shown that recombinant FARs of parasitic nematode species possess a strong binding activity to fatty acids and retinol (Rey-Burusco et al, 2015;Zhang et al, 2015;Qiao et al, 2016), and recent studies suggest that FARs are also capable of binding to a wide range of lipidic compounds such as diacylglycerol and phospholipids (Franchini et al, 2015). In animal-parasitic nematodes, FARs have been found within the excretory/secretory secretome, together with an extensive series of proteins that can interact with a range of activities of the nematode, to facilitate invasion and contribute to immune modulation of the host (Garofalo et al, 2002;Kennedy et al, 2013).…”

Section: Figurementioning

confidence: 99%

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Characterization and silencing of the fatty acid‐ and retinol‐binding Pp‐far‐1 gene in Pratylenchus penetrans

2017

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Fatty acid‐ and retinol‐binding proteins (FARs) are unique to nematodes, and are implicated in a wide range of metabolic and parasitic related functions. Along with the in silico analyses performed in this study, three different FAR members of this family were identified in Pratylenchus penetrans. The cDNA corresponding to the fatty acid‐ and retinol‐binding Pp‐far‐1 gene was cloned and herein characterized at the molecular level for the first time for this genus. The translated 185 amino acid sequence of P. penetrans FAR‐1 sequence, with a predicted molecular weight of 20.82 kDa and a pI of 5.49, shares highest sequence identity to FARs of other migratory nematodes of the Pratylenchidae family (90% to P. vulnus and 80% to Radopholus similis). In situ hybridization localizes Pp‐far‐1 transcripts in the hypodermis of the nematode. RT‐qPCR detected Pp‐far‐1 transcripts for all nematode developmental stages, with highest expression levels found in juveniles, adult females and adult males, respectively. Pp‐far‐1 is also highly expressed during infection and establishment of P. penetrans in roots of different host plants, such as corn, lily and soybean. The importance of Pp‐far‐1 was studied by in planta RNA interference (RNAi) assays using stable soybean hairy root lines. Targeting Pp‐far‐1 decreased expression of the nematode Pp‐far‐1 and significantly reduced the reproduction of nematodes, with a total of between 44% and 70% fewer nematodes in comparison to the average number of nematodes counted for control lines. The results indicate that suppressing the expression levels of Pp‐far‐1 can act as an effective target gene to control P. penetrans.

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Section: Discussionmentioning

confidence: 97%

Section: Figurementioning

confidence: 99%

Characterization and silencing of the fatty acid‐ and retinol‐binding Pp‐far‐1 gene in Pratylenchus penetrans

2017

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“…These data show that Ace-FAR-1 might help fatty acid uptake for cuticle integrity, egg generation, and embryo development [144]. On the contrary, Na-FAR-1 was localized in the male copulatory bursa and the adult worm intestine, indicating their roles in male reproduction and nutrient uptake [146]. FAR might promote the parasite infectivity and lower the intestinal mucosal IgA levels through decreasing the retinol amount required for repairing the intestinal injuries and upregulating Th2 cytokine response, respectively [143].…”

Section: Fatty-acid and Retinol-binding Proteinsmentioning

confidence: 85%

Twenty-five-year research progress in hookworm excretory/secretory products

et al. 2020

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Hookworm infection is a major public health problem that threatens about 500 million people throughout tropical areas of the world. Adult hookworms survive for many years in the host intestine, where they suck blood, causing iron deficiency anemia and malnutrition. Numerous molecules, named excretory/secretory (ES) products, are secreted by hookworm adults and/or larvae to aid in parasite survival and pathobiology. Although the molecular cloning and characterization of hookworm ES products began 25 years ago, the biological role and molecular nature of many of them are still unclear. Hookworm ES products, with distinct structures and functions, have been linked to many essential events in the disease pathogenesis. These events include host invasion and tissue migration, parasite nourishment and reproduction, and immune modulation. Several of these products represent promising vaccine targets for controlling hookworm disease and therapeutic targets for many inflammatory diseases. This review aims to summarize our present knowledge about hookworm ES products, including their role in parasite biology, host-parasite interactions, and as vaccine and pharmaceutical targets and to identify research gaps and future research directions in this field.

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“…The FAR-1 and FAR-2 proteins have six other isoforms described in C. elegans, which are localized in the cell membrane and are related to cell signaling and the immune response. Previous studies showed the bound capacity of these proteins in anthelmintics, such as albendazole, levamisole, abamectin, and praziquantel (REY-BURUSCO et al, 2015;QIAO et al, 2016). Thus, it is possible to suggest that FAR-1 and FAR-2 promote ivermectin resistance mechanisms by triggering biological signaling in addition to their possible role in recruiting fatty acids to contribute to the maintenance of energetic balance during the stress induced by the anthelmintic agent.…”

Section: Discussionmentioning

confidence: 99%

Differences in protein expression associated with ivermectin resistance in Caenorhabditis elegans

Sousa

Cunha

Silva

et al. 2019

Rev. Bras. Parasitol. Vet.

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The indiscriminate administration of synthetic anthelmintics such as ivermectin contributes to the selection of subpopulations capable of resisting the drugs’ effects. To understand the mechanisms of ivermectin resistance in Caenorhabditis elegans, this study attempted to identify molecular targets. C. elegans lineages that were sensitive and resistant to ivermectin were used. Collected nematodes were added to an extraction buffer and macerated in liquid nitrogen for protein extraction. The extracted proteins were separated according to molecular weight by SDS-PAGE to verify their integrity. Subsequently, proteins from both lineages were separated using two-dimensional electrophoresis. The gels were analyzed and the relevant spots were excised and identified by mass spectrometry (NanoESI-Q-TOF and MASCOT®) and subsequently assessed by GO enrichment and STRING® analyses. The increased expression of proteins associated with high metabolic activity, such as ATP-2 and ENOL-1, which are responsible for ATP synthesis, was observed. Furthermore, proteins with involvement in mediating muscular function (MLC-1, ACT-1, and PDI-2), signaling (FAR-1 and FAR-2), and embryo development (VHA-2) were identified. Protein interaction analysis indicated that the majority of the identified proteins in the resistant lineages participated in the same reaction triggered by ivermectin.

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Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from Necator americanus

Cited by 28 publications

References 71 publications

Characterization and silencing of the fatty acid‐ and retinol‐binding Pp‐far‐1 gene in Pratylenchus penetrans

Characterization and silencing of the fatty acid‐ and retinol‐binding Pp‐far‐1 gene in Pratylenchus penetrans

Twenty-five-year research progress in hookworm excretory/secretory products

Differences in protein expression associated with ivermectin resistance in Caenorhabditis elegans

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