Profiling G protein-coupled receptors of Fasciola hepatica identifies orphan rhodopsins unique to phylum Platyhelminthes

International Journal for Parasitology. Drugs and Drug Resistance
Paul McVeighAaron G Maule

Abstract

G protein-coupled receptors (GPCRs) are established drug targets. Despite their considerable appeal as targets for next-generation anthelmintics, poor understanding of their diversity and function in parasitic helminths has thwarted progress towards GPCR-targeted anti-parasite drugs. This study facilitates GPCR research in the liver fluke, Fasciola hepatica, by generating the first profile of GPCRs from the F. hepatica genome. Our dataset describes 147 high confidence GPCRs, representing the largest cohort of GPCRs, and the largest set of in silico ligand-receptor predictions, yet reported in any parasitic helminth. All GPCRs fall within the established GRAFS nomenclature; comprising three glutamate, 135 rhodopsin, two adhesion, five frizzled, one smoothened, and one secretin GPCR. Stringent annotation pipelines identified 18 highly diverged rhodopsins in F. hepatica that maintained core rhodopsin signatures, but lacked significant similarity with non-flatworm sequences, providing a new sub-group of potential flukicide targets. These facilitated identification of a larger cohort of 76 related sequences from available flatworm genomes, representing new members of existing groups (PROF1/Srfb, Rho-L, Rho-R, Srfa, Srfc) of flatworm...Continue Reading

Citations

Aug 14, 2019·PLoS Neglected Tropical Diseases·Shunyu LiSung-Jong Hong
Sep 11, 2019·Molecular Biology and Evolution·Young-Jun ChoiMakedonka Mitreva
Mar 7, 2020·Frontiers in Neuroscience·Luis Alfonso Yañez-Guerra, Maurice R Elphick
Mar 7, 2021·Animals : an Open Access Journal From MDPI·Alexandra KahlMartin Ganter
May 24, 2021·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Víctor Caña-BozadaF Neptalí Morales-Serna
Aug 5, 2021·ACS Chemical Neuroscience·Louise E AtkinsonAngela Mousley

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Datasets Mentioned

BETA
PRJEB6687
PRJNA179522

Methods Mentioned

BETA
RNA-Seq
dissection

Software Mentioned

CLANS
Cuffdiff
ncbi nr
MAFFT
Cufflinks
hmmbuild
PhyML
hClust
BLASTp BLAST +
Ensembl Compara

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