Abstract
Filarial nematodes, such as Brugia malayi, cause major health problems worldwide. The lack of a vaccine against B. malayi, combined with ineffective chemotherapy against the adult has prompted the examination of biogenic amine receptors (BARs) as possible targets for drug discovery. We employed bioinformatics to identify genes encoding putative B. malayi BARs. Surprisingly, the B. malayi genome contains half of the genes predicted to encode BARs in the genomes of free-living nematodes such as Caenorhabditis elegans or C. briggsae; however, all of the predicted B. malayi receptors have clear orthologues in C. elegans. The B. malayi genes encode each of the major BAR subclasses, including three serotonin, two dopamine and two tyramine/octopamine receptors and the structure of orthologous BAR genes is conserved. We find that potential G-protein coupling and ligand-specificity of individual BARs may be predicted by phylogenetic comparisons. Our results provide a framework for how G-protein coupled receptors may be targeted for drug development in medically important parasitic nematodes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 227-244 |
| Number of pages | 18 |
| Journal | Invertebrate Neuroscience |
| Volume | 7 |
| Issue number | 4 |
| DOIs | |
| State | Published - Dec 2007 |
Fingerprint
Keywords
- Brugia malayi
- Caenorhabditis briggsae
- Caenorhabditis elegans
- Dopamine
- G-protein coupling
- Octopamine
- Serotonin
- Tyramine
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Genes encoding putative biogenic amine receptors in the parasitic nematode Brugia malayi. / Smith, Katherine A.; Komuniecki, Richard W.; Ghedin, Elodie; Spiro, David; Gray, John.
In: Invertebrate Neuroscience, Vol. 7, No. 4, 12.2007, p. 227-244.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Genes encoding putative biogenic amine receptors in the parasitic nematode Brugia malayi
AU - Smith, Katherine A.
AU - Komuniecki, Richard W.
AU - Ghedin, Elodie
AU - Spiro, David
AU - Gray, John
PY - 2007/12
Y1 - 2007/12
N2 - Filarial nematodes, such as Brugia malayi, cause major health problems worldwide. The lack of a vaccine against B. malayi, combined with ineffective chemotherapy against the adult has prompted the examination of biogenic amine receptors (BARs) as possible targets for drug discovery. We employed bioinformatics to identify genes encoding putative B. malayi BARs. Surprisingly, the B. malayi genome contains half of the genes predicted to encode BARs in the genomes of free-living nematodes such as Caenorhabditis elegans or C. briggsae; however, all of the predicted B. malayi receptors have clear orthologues in C. elegans. The B. malayi genes encode each of the major BAR subclasses, including three serotonin, two dopamine and two tyramine/octopamine receptors and the structure of orthologous BAR genes is conserved. We find that potential G-protein coupling and ligand-specificity of individual BARs may be predicted by phylogenetic comparisons. Our results provide a framework for how G-protein coupled receptors may be targeted for drug development in medically important parasitic nematodes.
AB - Filarial nematodes, such as Brugia malayi, cause major health problems worldwide. The lack of a vaccine against B. malayi, combined with ineffective chemotherapy against the adult has prompted the examination of biogenic amine receptors (BARs) as possible targets for drug discovery. We employed bioinformatics to identify genes encoding putative B. malayi BARs. Surprisingly, the B. malayi genome contains half of the genes predicted to encode BARs in the genomes of free-living nematodes such as Caenorhabditis elegans or C. briggsae; however, all of the predicted B. malayi receptors have clear orthologues in C. elegans. The B. malayi genes encode each of the major BAR subclasses, including three serotonin, two dopamine and two tyramine/octopamine receptors and the structure of orthologous BAR genes is conserved. We find that potential G-protein coupling and ligand-specificity of individual BARs may be predicted by phylogenetic comparisons. Our results provide a framework for how G-protein coupled receptors may be targeted for drug development in medically important parasitic nematodes.
KW - Brugia malayi
KW - Caenorhabditis briggsae
KW - Caenorhabditis elegans
KW - Dopamine
KW - G-protein coupling
KW - Octopamine
KW - Serotonin
KW - Tyramine
UR - http://www.scopus.com/inward/record.url?scp=36448935302&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36448935302&partnerID=8YFLogxK
U2 - 10.1007/s10158-007-0058-y
DO - 10.1007/s10158-007-0058-y
M3 - Article
C2 - 18027007
AN - SCOPUS:36448935302
VL - 7
SP - 227
EP - 244
JO - Invertebrate Neuroscience
JF - Invertebrate Neuroscience
SN - 1354-2516
IS - 4
ER -