Cargando…

The repertoire of G protein-coupled receptors in the human parasite Schistosoma mansoni and the model organism Schmidtea mediterranea

BACKGROUND: G protein-coupled receptors (GPCRs) constitute one of the largest groupings of eukaryotic proteins, and represent a particularly lucrative set of pharmaceutical targets. They play an important role in eukaryotic signal transduction and physiology, mediating cellular responses to a divers...

Descripción completa

Detalles Bibliográficos
Autores principales: Zamanian, Mostafa, Kimber, Michael J, McVeigh, Paul, Carlson, Steve A, Maule, Aaron G, Day, Tim A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261222/
https://www.ncbi.nlm.nih.gov/pubmed/22145649
http://dx.doi.org/10.1186/1471-2164-12-596
_version_ 1782221576155955200
author Zamanian, Mostafa
Kimber, Michael J
McVeigh, Paul
Carlson, Steve A
Maule, Aaron G
Day, Tim A
author_facet Zamanian, Mostafa
Kimber, Michael J
McVeigh, Paul
Carlson, Steve A
Maule, Aaron G
Day, Tim A
author_sort Zamanian, Mostafa
collection PubMed
description BACKGROUND: G protein-coupled receptors (GPCRs) constitute one of the largest groupings of eukaryotic proteins, and represent a particularly lucrative set of pharmaceutical targets. They play an important role in eukaryotic signal transduction and physiology, mediating cellular responses to a diverse range of extracellular stimuli. The phylum Platyhelminthes is of considerable medical and biological importance, housing major pathogens as well as established model organisms. The recent availability of genomic data for the human blood fluke Schistosoma mansoni and the model planarian Schmidtea mediterranea paves the way for the first comprehensive effort to identify and analyze GPCRs in this important phylum. RESULTS: Application of a novel transmembrane-oriented approach to receptor mining led to the discovery of 117 S. mansoni GPCRs, representing all of the major families; 105 Rhodopsin, 2 Glutamate, 3 Adhesion, 2 Secretin and 5 Frizzled. Similarly, 418 Rhodopsin, 9 Glutamate, 21 Adhesion, 1 Secretin and 11 Frizzled S. mediterranea receptors were identified. Among these, we report the identification of novel receptor groupings, including a large and highly-diverged Platyhelminth-specific Rhodopsin subfamily, a planarian-specific Adhesion-like family, and atypical Glutamate-like receptors. Phylogenetic analysis was carried out following extensive gene curation. Support vector machines (SVMs) were trained and used for ligand-based classification of full-length Rhodopsin GPCRs, complementing phylogenetic and homology-based classification. CONCLUSIONS: Genome-wide investigation of GPCRs in two platyhelminth genomes reveals an extensive and complex receptor signaling repertoire with many unique features. This work provides important sequence and functional leads for understanding basic flatworm receptor biology, and sheds light on a lucrative set of anthelmintic drug targets.
format Online
Article
Text
id pubmed-3261222
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-32612222012-01-19 The repertoire of G protein-coupled receptors in the human parasite Schistosoma mansoni and the model organism Schmidtea mediterranea Zamanian, Mostafa Kimber, Michael J McVeigh, Paul Carlson, Steve A Maule, Aaron G Day, Tim A BMC Genomics Research Article BACKGROUND: G protein-coupled receptors (GPCRs) constitute one of the largest groupings of eukaryotic proteins, and represent a particularly lucrative set of pharmaceutical targets. They play an important role in eukaryotic signal transduction and physiology, mediating cellular responses to a diverse range of extracellular stimuli. The phylum Platyhelminthes is of considerable medical and biological importance, housing major pathogens as well as established model organisms. The recent availability of genomic data for the human blood fluke Schistosoma mansoni and the model planarian Schmidtea mediterranea paves the way for the first comprehensive effort to identify and analyze GPCRs in this important phylum. RESULTS: Application of a novel transmembrane-oriented approach to receptor mining led to the discovery of 117 S. mansoni GPCRs, representing all of the major families; 105 Rhodopsin, 2 Glutamate, 3 Adhesion, 2 Secretin and 5 Frizzled. Similarly, 418 Rhodopsin, 9 Glutamate, 21 Adhesion, 1 Secretin and 11 Frizzled S. mediterranea receptors were identified. Among these, we report the identification of novel receptor groupings, including a large and highly-diverged Platyhelminth-specific Rhodopsin subfamily, a planarian-specific Adhesion-like family, and atypical Glutamate-like receptors. Phylogenetic analysis was carried out following extensive gene curation. Support vector machines (SVMs) were trained and used for ligand-based classification of full-length Rhodopsin GPCRs, complementing phylogenetic and homology-based classification. CONCLUSIONS: Genome-wide investigation of GPCRs in two platyhelminth genomes reveals an extensive and complex receptor signaling repertoire with many unique features. This work provides important sequence and functional leads for understanding basic flatworm receptor biology, and sheds light on a lucrative set of anthelmintic drug targets. BioMed Central 2011-12-06 /pmc/articles/PMC3261222/ /pubmed/22145649 http://dx.doi.org/10.1186/1471-2164-12-596 Text en Copyright ©2011 Zamanian et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zamanian, Mostafa
Kimber, Michael J
McVeigh, Paul
Carlson, Steve A
Maule, Aaron G
Day, Tim A
The repertoire of G protein-coupled receptors in the human parasite Schistosoma mansoni and the model organism Schmidtea mediterranea
title The repertoire of G protein-coupled receptors in the human parasite Schistosoma mansoni and the model organism Schmidtea mediterranea
title_full The repertoire of G protein-coupled receptors in the human parasite Schistosoma mansoni and the model organism Schmidtea mediterranea
title_fullStr The repertoire of G protein-coupled receptors in the human parasite Schistosoma mansoni and the model organism Schmidtea mediterranea
title_full_unstemmed The repertoire of G protein-coupled receptors in the human parasite Schistosoma mansoni and the model organism Schmidtea mediterranea
title_short The repertoire of G protein-coupled receptors in the human parasite Schistosoma mansoni and the model organism Schmidtea mediterranea
title_sort repertoire of g protein-coupled receptors in the human parasite schistosoma mansoni and the model organism schmidtea mediterranea
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3261222/
https://www.ncbi.nlm.nih.gov/pubmed/22145649
http://dx.doi.org/10.1186/1471-2164-12-596
work_keys_str_mv AT zamanianmostafa therepertoireofgproteincoupledreceptorsinthehumanparasiteschistosomamansoniandthemodelorganismschmidteamediterranea
AT kimbermichaelj therepertoireofgproteincoupledreceptorsinthehumanparasiteschistosomamansoniandthemodelorganismschmidteamediterranea
AT mcveighpaul therepertoireofgproteincoupledreceptorsinthehumanparasiteschistosomamansoniandthemodelorganismschmidteamediterranea
AT carlsonstevea therepertoireofgproteincoupledreceptorsinthehumanparasiteschistosomamansoniandthemodelorganismschmidteamediterranea
AT mauleaarong therepertoireofgproteincoupledreceptorsinthehumanparasiteschistosomamansoniandthemodelorganismschmidteamediterranea
AT daytima therepertoireofgproteincoupledreceptorsinthehumanparasiteschistosomamansoniandthemodelorganismschmidteamediterranea
AT zamanianmostafa repertoireofgproteincoupledreceptorsinthehumanparasiteschistosomamansoniandthemodelorganismschmidteamediterranea
AT kimbermichaelj repertoireofgproteincoupledreceptorsinthehumanparasiteschistosomamansoniandthemodelorganismschmidteamediterranea
AT mcveighpaul repertoireofgproteincoupledreceptorsinthehumanparasiteschistosomamansoniandthemodelorganismschmidteamediterranea
AT carlsonstevea repertoireofgproteincoupledreceptorsinthehumanparasiteschistosomamansoniandthemodelorganismschmidteamediterranea
AT mauleaarong repertoireofgproteincoupledreceptorsinthehumanparasiteschistosomamansoniandthemodelorganismschmidteamediterranea
AT daytima repertoireofgproteincoupledreceptorsinthehumanparasiteschistosomamansoniandthemodelorganismschmidteamediterranea