Mechanism and function of Drosophila capa GPCR: a desiccation stress-responsive receptor with functional homology to human neuromedinU receptor.
PLoS One
; 7(1): e29897, 2012.
Article
in En
| MEDLINE
| ID: mdl-22253819
ABSTRACT
The capa peptide receptor, capaR (CG14575), is a G-protein coupled receptor (GPCR) for the D. melanogaster capa neuropeptides, Drm-capa-1 and -2 (capa-1 and -2). To date, the capa peptide family constitutes the only known nitridergic peptides in insects, so the mechanisms and physiological function of ligand-receptor signalling of this peptide family are of interest. Capa peptide induces calcium signaling via capaR with EC50 values for capa-1â=â3.06 nM and capa-2â=â4.32 nM. capaR undergoes rapid desensitization, with internalization via a b-arrestin-2 mediated mechanism but is rapidly re-sensitized in the absence of capa-1. Drosophila capa peptides have a C-terminal -FPRXamide motif and insect-PRXamide peptides are evolutionarily related to vertebrate peptide neuromedinU (NMU). Potential agonist effects of human NMU-25 and the insect -PRLamides [Drosophila pyrokinins Drm-PK-1 (capa-3), Drm-PK-2 and hugin-gamma [hugg]] against capaR were investigated. NMU-25, but not hugg nor Drm-PK-2, increases intracellular calcium ([Ca²âº]i) levels via capaR. In vivo, NMU-25 increases [Ca²âº]i and fluid transport by the Drosophila Malpighian (renal) tubule. Ectopic expression of human NMU receptor 2 in tubules of transgenic flies results in increased [Ca²âº]i and fluid transport. Finally, anti-porcine NMU-8 staining of larval CNS shows that the most highly immunoreactive cells are capa-producing neurons. These structural and functional data suggest that vertebrate NMU is a putative functional homolog of Drm-capa-1 and -2. capaR is almost exclusively expressed in tubule principal cells; cell-specific targeted capaR RNAi significantly reduces capa-1 stimulated [Ca²âº]i and fluid transport. Adult capaR RNAi transgenic flies also display resistance to desiccation. Thus, capaR acts in the key fluid-transporting tissue to regulate responses to desiccation stress in the fly.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Stress, Physiological
/
Sequence Homology, Amino Acid
/
Receptors, Neurotransmitter
/
Drosophila Proteins
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Receptors, G-Protein-Coupled
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Desiccation
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Drosophila melanogaster
Limits:
Animals
/
Humans
Language:
En
Journal:
PLoS One
Journal subject:
CIENCIA
/
MEDICINA
Year:
2012
Document type:
Article
Affiliation country:
United kingdom