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Receptor deorphanization in an echinoderm reveals kisspeptin evolution and relationship with SALMFamide neuropeptides

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Escudero Castelán, Nayeli, Semmens, Dean C., Guerra, Luis Alfonso Yañez, Zandawala, Meet, dos Reis, Mario, Slade, Susan E., Scrivens, James H., Zampronio, Cleidiane G., Jones, Alexandra M., Mirabeau, Olivier and Elphick, Maurice R. (2022) Receptor deorphanization in an echinoderm reveals kisspeptin evolution and relationship with SALMFamide neuropeptides. BMC Biology, 20 (1). 187. doi:10.1186/s12915-022-01387-z

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Official URL: https://doi.org/10.1186/s12915-022-01387-z

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Abstract

Background: Kisspeptins are neuropeptides that regulate reproductive maturation in mammals via G-protein-coupled receptor-mediated stimulation of gonadotropin-releasing hormone secretion from the hypothalamus. Phylogenetic analysis of kisspeptin-type receptors indicates that this neuropeptide signaling system originated in a common ancestor of the Bilateria, but little is known about kisspeptin signaling in invertebrates.
Results: Contrasting with the occurrence of a single kisspeptin receptor in mammalian species, here, we report the discovery of an expanded family of eleven kisspeptin-type receptors in a deuterostome invertebrate — the starfish Asterias rubens (phylum Echinodermata). Furthermore, neuropeptides derived from four precursor proteins were identified as ligands for six of these receptors. One or more kisspeptin-like neuropeptides derived from two precursor proteins (ArKPP1, ArKPP2) act as ligands for four A. rubens kisspeptin-type receptors (ArKPR1,3,8,9). Furthermore, a family of neuropeptides that act as muscle relaxants in echinoderms (SALMFamides) are ligands for two A. rubens kisspeptin-type receptors (ArKPR6,7). The SALMFamide neuropeptide S1 (or ArS1.4) and a ‘cocktail’ of the seven neuropeptides derived from the S1 precursor protein (ArS1.1-ArS1.7) act as ligands for ArKPR7. The SALMFamide neuropeptide S2 (or ArS2.3) and a ‘cocktail’ of the eight neuropeptides derived from the S2 precursor protein (ArS2.1-ArS2.8) act as ligands for ArKPR6.
Conclusions: Our findings reveal a remarkable diversity of neuropeptides that act as ligands for kisspeptin-type receptors in starfish and provide important new insights into the evolution of kisspeptin signaling. Furthermore, the discovery of the hitherto unknown relationship of kisspeptins with SALMFamides, neuropeptides that were discovered in starfish prior to the identification of kisspeptins in mammals, presents a radical change in perspective for research on kisspeptin signaling.

Item Type: Journal Article
Subjects: Q Science > QL Zoology
Q Science > QP Physiology
Divisions: Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- )
SWORD Depositor: Library Publications Router
Library of Congress Subject Headings (LCSH): Neuropeptides, Kisspeptin neurons, Asterias rubens, Echinodermata
Journal or Publication Title: BMC Biology
Publisher: BioMed Central Ltd.
ISSN: 1741-7007
Official Date: 24 August 2022
Dates:
DateEvent
24 August 2022Published
9 August 2022Accepted
Volume: 20
Number: 1
Article Number: 187
DOI: 10.1186/s12915-022-01387-z
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
RPG-2013–351Leverhulme Trusthttp://dx.doi.org/10.13039/501100000275
RPG-2016–353Leverhulme Trusthttp://dx.doi.org/10.13039/501100000275
BB/ M001644/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/M001032/1[BBSRC] Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
471864Consejo Nacional de Ciencia y Tecnologíahttp://dx.doi.org/10.13039/501100003141
418612Consejo Nacional de Ciencia y Tecnologíahttp://dx.doi.org/10.13039/501100003141

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