The structure of the FMRFamide receptor and activity of the cardioexcitatory neuropeptide are conserved in mosquito.
Numerous peptides are structurally related to the cardioexcitatory tetrapeptide FMRFamide. One subgroup of FMRFamide-related peptides (FaRPs) contains an FMRFamide C terminus. Searches of the Drosophila melanogaster genome database identified the first invertebrate FMRFamide G-protein coupled receptor (GPCR), DrmFMRFa-R (Cazzamali and Grimmelikhuijzen, Meeusen et al., 2002). In order to explore molecular mechanisms involved in FMRFamide signal transduction we identified a receptor from the malaria mosquito Anopheles gambiae genome (Holt et al., 2002), AngFMRFa-R, and compared its structure to DrmFMRFa-R. The cytoplasmic loops, extracellular loops, and transmembrane regions are highly conserved between these two FMRFamide receptors. Another subgroup of FaRPs is the sulfakinins which are represented by the consensus structure -XDYGHMRFamide, where X is D or E (Nichols, 2003). We compared AngFMRFa-R and DrmFMRFa-R to the A. gambiae sulfakinin receptors, ASK-R1 and ASK-R2 ( Duttlinger et al., 2003), and the D. melanogaster sulfakinin receptors, DSK-R1 and DSK-R2 Brody and Cravchik, 2000; Hewes and Taghert, 2001 ). The cytoplasmic loops, extracellular loops, and the transmembrane regions are not highly conserved between the FMRFamide and sulfakinin receptors. In order to explore the role of FMRFamide in mosquito biology we measured the effect of the tetrapeptide on in vivo heart rate. The tetrapeptide increased the frequency of spontaneous contractions of the larval mosquito heart and, thus, increased heart rate. These data support the conclusion that the structure of the FMRFamide receptor and activity of the cardioexcitatory FMRFamide neuropeptide are conserved in mosquito.
Biological Chemistry Department, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Amanda
A
Duttlinger
Melissa
M
Mispelon
Ruthann
R
Nichols
D000330:Aedes / Q000254:growth & development / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D030541:Databases, Genetic; D019204:GTP-Binding Proteins / Q000378:metabolism; D016678:Genome; D006321:Heart / Q000254:growth & development / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D007814:Larva / Q000502:physiology; D008969:Molecular Sequence Data; D009200:Myocardial Contraction / Q000502:physiology; D009479:Neuropeptides / Q000502:physiology*; D018010:Receptors, Invertebrate Peptide / Q000737:chemistry* / Q000187:drug effects*
C055209:FMRFamide receptor; D009479:Neuropeptides; D018010:Receptors, Invertebrate Peptide; D019204:GTP-Binding Proteins