Past and Future Strategies for GPCR Deorphanization

Levoye, Angélique; Clément, Nathalie; Tenconi, Elodie; Jockers, Ralf

doi:10.1002/9780470627327.ch7

Cited by 1 publication

(2 citation statements)

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“…The designation orphan is used to describe receptors that belong to the GPCR superfamily but whose ligand is unknown or cannot be predicted based on sequence homology, as is the case with most of the aminergic GPCRs of schistosomes. Orphan GPCRs are of considerable interest as targets for drug discovery in human pharmacology (Lin and Civelli 2004) and the efforts to identify (or deorphanize) these receptors are driving the development of new technologies for GPCR analysis (Levoye et al 2010). These technologies can now be used to accelerate the pace of GPCR discovery in other systems, including schistosomes.…”

Section: Strategies For ''Deorphanization'' Of Novel Ba-like Receptorsmentioning

confidence: 99%

“…4 Functional genomics of biogenic amine G-protein-coupled receptors (GPCRs) in schistosomes. Schematic representation of various strategies for deorphanization and characterization of schistosome GPCRs, as discussed in the text (adapted from Levoye et al 2010). Erk Extracellular signal-regulated kinase protein (Ga15 or Ga16), which enables the receptor to generate a signal upon agonist activation, regardless of the natural G-protein coupling specificity.…”

Section: Gpcr Activity Assaysmentioning

confidence: 99%

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Biogenic amines and the control of neuromuscular signaling in schistosomes

2012

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Biogenic amines are small cationic monoamines that function broadly as neurotransmitters and/or neuromodulators in every animal phylum. They include such ubiquitous substances as serotonin, dopamine and invertebrate-specific phenolamines (tyramine, octopamine), among others. Biogenic amines are important neuroactive agents in all the flatworms, including blood flukes of the genus Schistosoma, the etiological agents of human schistosomiasis. A large body of evidence spanning nearly five decades identifies biogenic amines as major modulators of neuromuscular function in schistosomes, controlling movement, attachment to the host and other fundamental behaviors. Recent advances in schistosome genomics have made it possible to dissect the molecular mechanisms responsible for these effects and to identify the proteins involved. These efforts have already provided important new information about the mode of action of amine transmitters in the parasite. Moreover, these advances are continuing, as the field moves into a post-genomics era, and new molecular tools for gene and protein analysis are becoming available. Here, we review the current status of this research and discuss future prospects. In particular, we focus our attention on the receptors that mediate biogenic amine activity, their structural characteristics, functional properties and "druggability" potential. One of the themes that will emerge from this discussion is that schistosomes have a rich diversity of aminergic receptors, many of which share little sequence homology with those of the human host, making them ideally suited for selective drug targeting. Strategies for the characterization of these important parasite proteins will be discussed.

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Section: Strategies For ''Deorphanization'' Of Novel Ba-like Receptorsmentioning

confidence: 99%

Section: Gpcr Activity Assaysmentioning

confidence: 99%