Pharmacological evaluation of MRAP proteins on Xenopus neural melanocortin signaling.
J Cell Physiol
; 236(9): 6344-6361, 2021 09.
Article
en En
| MEDLINE
| ID: mdl-33521982
ABSTRACT
Melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R), two neural G protein-coupled receptors are known to be functionally critical for energy balance in vertebrates. As allosteric regulators of melanocortin receptors, melanocortin accessory proteins (MRAPs) are also involved in energy homeostasis. The interaction of MRAPs and melanocortin signaling was previously shown in mammals and zebrafish, but nothing had been reported in amphibians. As the basal class of tetrapods, amphibians occupy a phylogenetic transition between teleosts and terrestrial animals. Here we examined the evolutionary conservation of MC3R, MC4R, and MRAPs between diploid Xenopus tropicalis (xt-) and other chordates and investigated the pharmacological regulatory properties of MRAPs on the neural MC3R and MC4R signaling. Our results showed that xtMRAP and xtMRAP2 both exerted robust potentiation effect on agonist (α-MSH and adrenocorticotropin [ACTH]) induced activation and modulated the basal activity and cell surface translocation of xtMC3R and xtMC4R. In addition, the presence of two accessory proteins could convert xtMC3R and xtMC4R into ACTH-preferred receptors. These findings suggest that the presence of MRAPs exhibits fine control over the pharmacological activities of the neuronal MC3R and MC4R signaling in the Xenopus tropicalis, which is physiologically relevant with the complicated transition of feeding behaviors during their life history.
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Texto completo:
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Base de datos:
MEDLINE
Asunto principal:
Xenopus
/
Transducción de Señal
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Proteínas de Xenopus
/
Melanocortinas
/
Neuronas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Cell Physiol
Año:
2021
Tipo del documento:
Article
País de afiliación:
China