{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T06:13:16Z","timestamp":1775542396761,"version":"3.50.1"},"reference-count":62,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":36,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003971","name":"Islamic Development Bank","doi-asserted-by":"publisher","award":["600042746"],"award-info":[{"award-number":["600042746"]}],"id":[{"id":"10.13039\/501100003971","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009148","name":"Queen Mary University of London","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009148","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Humanidades, Ciencias y Tecnolog\u00edas","doi-asserted-by":"publisher","award":["418612"],"award-info":[{"award-number":["418612"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000275","name":"Leverhulme Trust","doi-asserted-by":"publisher","award":["RPG-2016-353"],"award-info":[{"award-number":["RPG-2016-353"]}],"id":[{"id":"10.13039\/501100000275","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/M001644\/1"],"award-info":[{"award-number":["BB\/M001644\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The neurohormone kisspeptin regulates reproductive maturation and function in mammals by stimulating hypothalamic production and release of gonadotropin-releasing hormone. However, little is known about kisspeptin-type neuropeptide function in invertebrates and the evolution of kisspeptin signalling as a regulator of physiological processes. Here, we address these issues in a deuterostome invertebrate \u2014 the starfish\n                      <jats:italic>Asterias rubens<\/jats:italic>\n                      (phylum Echinodermata).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Unlike mammals that have one kisspeptin precursor protein, in\n                      <jats:italic>A. rubens<\/jats:italic>\n                      , two precursor proteins (ArKPP1, ArKPP2) give rise to four kisspeptin-type neuropeptides (ArKP1.1, ArKP1.2, ArKP2.1, ArKP2.2). Use of mRNA in situ hybridisation and immunohistochemistry revealed widespread but different patterns of expression of KP1-type and KP2-type neuropeptides in the central nervous system, locomotory organs, sensory organs, reproductive system, and digestive system of\n                      <jats:italic>A. rubens<\/jats:italic>\n                      . In vitro experiments revealed that KP1-type and KP2-type neuropeptides have opposing myoinhibitory and myoexcitatory effects, respectively, on starfish gonad and stomach preparations. When injected in vivo, both KP1-type and KP2-type neuropeptides trigger stomach eversion and ArKP1.2 affects righting behaviour.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study has revealed that kisspeptin-type neuropeptides are evolutionarily ancient and pleiotropic regulators of processes that extend beyond reproductive physiology. Furthermore, the excitatory actions of ArKP2.2 in\n                      <jats:italic>A. rubens<\/jats:italic>\n                      are consistent with stimulatory effects of kisspeptins in vertebrates; accordingly, ArKP2.2 acts as a ligand for a receptor (ArKPR3) that is closely related to vertebrate kisspeptin receptors. On the other hand, phylogenetic analysis of receptors for ArKP1.1 and ArKP1.2 indicates that inhibitory kisspeptin signalling either evolved uniquely in Ambulacraria (echinoderms, hemichordates) or originated in Urbilateria but was lost in chordates.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12915-026-02555-1","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T06:33:59Z","timestamp":1771396439000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evolution of neurohormone function revealed by actions\u00a0of kisspeptin-type peptides in an echinoderm"],"prefix":"10.1186","volume":"24","author":[{"given":"Tabinda","family":"Islam","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis A.","family":"Ya\u00f1ez-Guerra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dean C.","family":"Semmens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riley T.","family":"Beskeen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela","family":"Egertov\u00e1","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9169-0048","authenticated-orcid":false,"given":"Maurice R.","family":"Elphick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"2555_CR1","doi-asserted-by":"crossref","unstructured":"Chakraborty AP, Banerjee AA. Kisspeptin isoforms: versatile players in reproduction and beyond. J Mol Endocrinol. 2025;75(1):e250001.","DOI":"10.1530\/JME-25-0001"},{"key":"2555_CR2","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/bs.vh.2024.06.005","volume":"127","author":"KP Joy","year":"2025","unstructured":"Joy KP, Chaube R. Kisspeptin control of hypothalamus-pituitary-ovarian functions. Vitam Horm. 2025;127:153\u2013206.","journal-title":"Vitam Horm"},{"issue":"17","key":"2555_CR3","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1056\/NEJMoa035322","volume":"349","author":"SB Seminara","year":"2003","unstructured":"Seminara SB, Messager S, Chatzidaki EE, Thresher RR, Acierno JS, Shagoury JK, et al. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003;349(17):1614\u201327.","journal-title":"N Engl J Med"},{"key":"2555_CR4","doi-asserted-by":"crossref","unstructured":"d'Anglemont de Tassigny X, Fagg LA, Dixon JP, Day K, Leitch HG, Hendrick AG, et al. Hypogonadotropic hypogonadism in mice lacking a functional Kiss1 gene. Proc Natl Acad Sci. 2007;104(25):10714\u20139.","DOI":"10.1073\/pnas.0704114104"},{"issue":"19","key":"2555_CR5","doi-asserted-by":"publisher","first-page":"10972","DOI":"10.1073\/pnas.1834399100","volume":"100","author":"N De Roux","year":"2003","unstructured":"De Roux N, Genin E, Carel J-C, Matsuda F, Chaussain J-L, Milgrom E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A. 2003;100(19):10972\u20136.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"31","key":"2555_CR6","doi-asserted-by":"publisher","first-page":"28969","DOI":"10.1074\/jbc.M102743200","volume":"276","author":"AI Muir","year":"2001","unstructured":"Muir AI, Chamberlain L, Elshourbagy NA, Michalovich D, Moore DJ, Calamari A, et al. AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. J Biol Chem. 2001;276(31):28969\u201375.","journal-title":"J Biol Chem"},{"issue":"6837","key":"2555_CR7","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/35079135","volume":"411","author":"T Ohtaki","year":"2001","unstructured":"Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A, Kanehashi K, et al. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature. 2001;411(6837):613\u20137.","journal-title":"Nature"},{"issue":"37","key":"2555_CR8","doi-asserted-by":"publisher","first-page":"34631","DOI":"10.1074\/jbc.M104847200","volume":"276","author":"M Kotani","year":"2001","unstructured":"Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, et al. The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem. 2001;276(37):34631\u20136.","journal-title":"J Biol Chem"},{"key":"2555_CR9","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2014.00093","volume":"5","author":"MR Elphick","year":"2014","unstructured":"Elphick MR, Mirabeau O. The evolution and variety of RFamide-type neuropeptides: insights from Deuterostomian invertebrates. Front Endocrinol (Lausanne). 2014;5:93.","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"3","key":"2555_CR10","doi-asserted-by":"publisher","first-page":"T101","DOI":"10.1530\/JME-13-0224","volume":"52","author":"J Pasquier","year":"2014","unstructured":"Pasquier J, Kamech N, Lafont AG, Vaudry H, Rousseau K, Dufour S. Molecular evolution of GPCRs: kisspeptin\/kisspeptin receptors. J Mol Endocrinol. 2014;52(3):T101\u201317.","journal-title":"J Mol Endocrinol"},{"key":"2555_CR11","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2012.00173","volume":"3","author":"J Pasquier","year":"2012","unstructured":"Pasquier J, Lafont AG, Tostivint H, Vaudry H, Rousseau K, Dufour S. Comparative evolutionary histories of kisspeptins and kisspeptin receptors in vertebrates reveal both parallel and divergent features. Front Endocrinol (Lausanne). 2012;3:173.","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"1","key":"2555_CR12","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-022-01387-z","volume":"20","author":"N Escudero Castel\u00e1n","year":"2022","unstructured":"Escudero Castel\u00e1n N, Semmens DC, Ya\u00f1ez Guerra LA, Zandawala M, Dos Reis M, Slade SE, et al. Receptor deorphanization in an echinoderm reveals kisspeptin evolution and relationship with SALMFamide neuropeptides. BMC Biol. 2022;20(1):187.","journal-title":"BMC Biol"},{"issue":"1","key":"2555_CR13","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2148-14-30","volume":"14","author":"J Pasquier","year":"2014","unstructured":"Pasquier J, Lafont AG, Rousseau K, Qu\u00e9rat B, Chemineau P, Dufour S. Looking for the bird Kiss: evolutionary scenario in sauropsids. BMC Evol Biol. 2014;14(1):30.","journal-title":"BMC Evol Biol"},{"issue":"22","key":"2555_CR14","doi-asserted-by":"publisher","first-page":"E2028","DOI":"10.1073\/pnas.1219956110","volume":"110","author":"O Mirabeau","year":"2013","unstructured":"Mirabeau O, Joly JS. Molecular evolution of peptidergic signaling systems in bilaterians. Proc Natl Acad Sci U S A. 2013;110(22):E2028\u201337.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"2555_CR15","doi-asserted-by":"publisher","first-page":"1461","DOI":"10.1210\/en.2016-1848","volume":"158","author":"P Wang","year":"2017","unstructured":"Wang P, Wang M, Ji G, Yang S, Zhang S, Liu Z. Demonstration of a functional kisspeptin\/kisspeptin receptor system in amphioxus with implications for origin of neuroendocrine regulation. Endocrinology. 2017;158(5):1461\u201373.","journal-title":"Endocrinology"},{"issue":"21","key":"2555_CR16","doi-asserted-by":"publisher","first-page":"8702","DOI":"10.1073\/pnas.1221833110","volume":"110","author":"G J\u00e9kely","year":"2013","unstructured":"J\u00e9kely G. Global view of the evolution and diversity of metazoan neuropeptide signaling. Proc Natl Acad Sci U S A. 2013;110(21):8702\u20137.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"2555_CR17","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.150224","volume":"6","author":"DC Semmens","year":"2016","unstructured":"Semmens DC, Mirabeau O, Moghul I, Pancholi MR, Wurm Y, Elphick MR. Transcriptomic identification of starfish neuropeptide precursors yields new insights into neuropeptide evolution. Open Biol. 2016;6(2):150224.","journal-title":"Open Biol"},{"issue":"1","key":"2555_CR18","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-019-0680-2","volume":"17","author":"EA Odekunle","year":"2019","unstructured":"Odekunle EA, Semmens DC, Martynyuk N, Tinoco AB, Garewal AK, Patel RR, et al. Ancient role of vasopressin\/oxytocin-type neuropeptides as regulators of feeding revealed in an echinoderm. BMC Biol. 2019;17(1):60.","journal-title":"BMC Biol"},{"issue":"1","key":"2555_CR19","doi-asserted-by":"publisher","DOI":"10.1002\/cne.25585","volume":"532","author":"VM Pi\u00f1on Gonzalez","year":"2024","unstructured":"Pi\u00f1on Gonzalez VM, Feng Y, Egertov\u00e1 M, Elphick MR. Neuropeptide expression and action in the reproductive system of the starfish Asterias rubens. J Comp Neurol. 2024;532(1):e25585.","journal-title":"J Comp Neurol"},{"key":"2555_CR20","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1098\/rspb.1999.0847","volume":"266","author":"R Melarange","year":"1999","unstructured":"Melarange R, Potton DJ, Thorndyke MC, Elphick MR. SALMFamide neuropeptides cause relaxation and eversion of the cardiac stomach in starfish. Proc Biol Sci. 1999;266:1785\u20139.","journal-title":"Proc Biol Sci"},{"issue":"12","key":"2555_CR21","doi-asserted-by":"publisher","first-page":"2519","DOI":"10.1242\/jeb.198.12.2519","volume":"198","author":"MR Elphick","year":"1995","unstructured":"Elphick MR, Newman SJ, Thorndyke MC. Distribution and action of SALMFamide neuropeptides in the starfish Asterias rubens. J Exp Biol. 1995;198(12):2519\u201325.","journal-title":"J Exp Biol"},{"key":"2555_CR22","doi-asserted-by":"crossref","unstructured":"Tinoco AB, Barreiro-Iglesias A, Ya\u00f1ez Guerra LA, Delroisse J, Zhang Y, Gunner EF, et al. Ancient role of sulfakinin\/cholecystokinin-type signalling in inhibitory regulation of feeding processes revealed in an echinoderm. Elife. 2021;10:e65667.","DOI":"10.7554\/eLife.65667"},{"issue":"Pt 21","key":"2555_CR23","first-page":"4047","volume":"216","author":"DC Semmens","year":"2013","unstructured":"Semmens DC, Dane RE, Pancholi MR, Slade SE, Scrivens JH, Elphick MR. Discovery of a novel neurophysin-associated neuropeptide that triggers cardiac stomach contraction and retraction in starfish. J Exp Biol. 2013;216(Pt 21):4047\u201353.","journal-title":"J Exp Biol"},{"key":"2555_CR24","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.925206","volume":"13","author":"Q Xie","year":"2022","unstructured":"Xie Q, Kang Y, Zhang C, Xie Y, Wang C, Liu J, et al. The role of kisspeptin in the control of the hypothalamic-pituitary-gonadal axis and reproduction. Front Endocrinol (Lausanne). 2022;13:925206.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2555_CR25","doi-asserted-by":"crossref","unstructured":"Zhang H, Zhang B, Qin G, Li S, Lin Q. The roles of the kisspeptin system in the reproductive physiology of the lined seahorse (Hippocampus erectus), an ovoviviparous fish with male pregnancy. Front Neurosci. 2018;12:940.","DOI":"10.3389\/fnins.2018.00940"},{"issue":"1","key":"2555_CR26","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.peptides.2008.06.016","volume":"30","author":"ML Gottsch","year":"2009","unstructured":"Gottsch ML, Clifton DK, Steiner RA. From KISS1 to kisspeptins: an historical perspective and suggested nomenclature. Peptides. 2009;30(1):4\u20139.","journal-title":"Peptides"},{"key":"2555_CR27","doi-asserted-by":"crossref","unstructured":"Li X, Liang C, Yan Y. Novel insight into the role of the Kiss1\/GPR54 system in energy metabolism in major metabolic organs. Cells. 2022;11(19):3148.","DOI":"10.3390\/cells11193148"},{"issue":"5","key":"2555_CR28","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1086\/BBLv24n5p362","volume":"24","author":"LJ Cole","year":"1913","unstructured":"Cole LJ. Experiments on co-ordination and righting in the starfish. Biol Bull. 1913;24(5):362\u20139.","journal-title":"Biol Bull"},{"issue":"587","key":"2555_CR29","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1098\/rstb.1946.0003","volume":"232","author":"JE Smith","year":"1946","unstructured":"Smith JE. The mechanics and innervation of the starfish tube foot-ampulla system. Philos Trans R Soc Lond B Biol Sci. 1946;232(587):279\u2013310.","journal-title":"Philos Trans R Soc Lond B Biol Sci"},{"issue":"1010","key":"2555_CR30","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1098\/rspb.1967.0053","volume":"168","author":"JLS Cobb","year":"1967","unstructured":"Cobb JLS. The innervation of the ampulla of the tube foot in the starfish Astropecten irregularis. Proc R Soc Lond B Biol Sci. 1967;168(1010):91\u20139.","journal-title":"Proc R Soc Lond B Biol Sci"},{"issue":"13","key":"2555_CR31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2420966122","volume":"122","author":"W Huang","year":"2025","unstructured":"Huang W, Zhong X, Zampronio CG, Bottrill AR, Jones KGE, Tinoco AB, et al. Discovery and functional characterization of a bombesin-type neuropeptide signaling system in an invertebrate. Proc Natl Acad Sci U S A. 2025;122(13):e2420966122.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2555_CR32","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2017.00259","volume":"8","author":"S Tian","year":"2017","unstructured":"Tian S, Egertov\u00e1 M, Elphick MR. Functional characterization of paralogous gonadotropin-releasing hormone-type and corazonin-type neuropeptides in an echinoderm. Front Endocrinol (Lausanne). 2017;8:259.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2555_CR33","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00507","volume":"9","author":"AB Tinoco","year":"2018","unstructured":"Tinoco AB, Semmens DC, Patching EC, Gunner EF, Egertov\u00e1 M, Elphick MR. Characterization of NGFFYamide signaling in starfish reveals roles in regulation of feeding behavior and locomotory systems. Front Endocrinol (Lausanne). 2018;9:507.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2555_CR34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2113589119","author":"Y Zhang","year":"2022","unstructured":"Zhang Y, Ya\u00f1ez-Guerra LA, Tinoco AB, Escudero Castel\u00e1n N, Egertov\u00e1 M, Elphick MR. Somatostatin-type and allatostatin-C-type neuropeptides are paralogous and have opposing myoregulatory roles in an echinoderm. Proc Natl Acad Sci U S A. 2022. https:\/\/doi.org\/10.1073\/pnas.2113589119.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"2555_CR35","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-019-0511-x","volume":"17","author":"Y Cao","year":"2019","unstructured":"Cao Y, Li Z, Jiang W, Ling Y, Kuang H. Reproductive functions of kisspeptin\/KISS1R systems in the periphery. Reprod Biol Endocrinol. 2019;17(1):65.","journal-title":"Reprod Biol Endocrinol"},{"issue":"3","key":"2555_CR36","doi-asserted-by":"publisher","first-page":"1235","DOI":"10.1152\/physrev.00037.2010","volume":"92","author":"L Pinilla","year":"2012","unstructured":"Pinilla L, Aguilar E, Dieguez C, Millar RP, Tena-Sempere M. Kisspeptins and reproduction: physiological roles and regulatory mechanisms. Physiol Rev. 2012;92(3):1235\u2013316.","journal-title":"Physiol Rev"},{"issue":"6","key":"2555_CR37","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1262\/jrd.2018-110","volume":"64","author":"Y Uenoyama","year":"2018","unstructured":"Uenoyama Y, Inoue N, Maeda KI, Tsukamura H. The roles of kisspeptin in the mechanism underlying reproductive functions in mammals. J Reprod Dev. 2018;64(6):469\u201376.","journal-title":"J Reprod Dev"},{"issue":"5","key":"2555_CR38","doi-asserted-by":"publisher","first-page":"858","DOI":"10.1002\/cne.24371","volume":"526","author":"M Lin","year":"2018","unstructured":"Lin M, Egertov\u00e1 M, Zampronio CG, Jones AM, Elphick MR. Functional characterization of a second pedal peptide\/orcokinin-type neuropeptide signaling system in the starfish Asterias rubens. J Comp Neurol. 2018;526(5):858\u201376.","journal-title":"J Comp Neurol"},{"issue":"9","key":"2555_CR39","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.200172","volume":"10","author":"Y Zhang","year":"2020","unstructured":"Zhang Y, Ya\u00f1ez Guerra LA, Egertov\u00e1 M, Zampronio CG, Jones AM, Elphick MR. Molecular and functional characterization of somatostatin-type signalling in a deuterostome invertebrate. Open Biol. 2020;10(9):200172.","journal-title":"Open Biol"},{"issue":"18","key":"2555_CR40","doi-asserted-by":"publisher","first-page":"3890","DOI":"10.1002\/cne.24309","volume":"525","author":"M Lin","year":"2017","unstructured":"Lin M, Egertov\u00e1 M, Zampronio CG, Jones AM, Elphick MR. Pedal peptide\/orcokinin-type neuropeptide signaling in a deuterostome: the anatomy and pharmacology of starfish myorelaxant peptide in Asterias rubens. J Comp Neurol. 2017;525(18):3890\u2013917.","journal-title":"J Comp Neurol"},{"issue":"2","key":"2555_CR41","doi-asserted-by":"publisher","first-page":"157","DOI":"10.2307\/1538604","volume":"107","author":"JM Anderson","year":"1954","unstructured":"Anderson JM. Studies on the cardiac stomach of the starfish, Asterias forbesi. Biol Bull. 1954;107(2):157\u201373.","journal-title":"Biol Bull"},{"issue":"1","key":"2555_CR42","doi-asserted-by":"publisher","DOI":"10.1186\/s12915-022-01491-0","volume":"20","author":"M J\u00f6nsson","year":"2022","unstructured":"J\u00f6nsson M, Morin M, Wang CK, Craik DJ, Degnan SM, Degnan BM. Sex-specific expression of pheromones and other signals in gravid starfish. BMC Biol. 2022;20(1):288.","journal-title":"BMC Biol"},{"key":"2555_CR43","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.jprot.2017.05.026","volume":"165","author":"MK Smith","year":"2017","unstructured":"Smith MK, Wang T, Suwansa-Ard S, Motti CA, Elizur A, Zhao M, et al. The neuropeptidome of the crown-of-thorns starfish, Acanthaster planci. J Proteomics. 2017;165:61\u20138.","journal-title":"J Proteomics"},{"key":"2555_CR44","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2022.1006594","volume":"16","author":"A Aleotti","year":"2022","unstructured":"Aleotti A, Wilkie IC, Ya\u00f1ez-Guerra LA, Gattoni G, Rahman TA, Wademan RF, et al. Discovery and functional characterization of neuropeptides in crinoid echinoderms. Front Neurosci. 2022;16:1006594.","journal-title":"Front Neurosci"},{"issue":"1","key":"2555_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-45271-3","volume":"9","author":"M Chen","year":"2019","unstructured":"Chen M, Talarovicova A, Zheng Y, Storey KB, Elphick MR. Neuropeptide precursors and neuropeptides in the sea cucumber Apostichopus japonicus: a genomic, transcriptomic and proteomic analysis. Sci Rep. 2019;9(1):8829.","journal-title":"Sci Rep"},{"key":"2555_CR46","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.170129","author":"M Zandawala","year":"2017","unstructured":"Zandawala M, Moghul I, Ya\u00f1ez Guerra LA, Delroisse J, Abylkassimova N, Hugall AF, et al. Discovery of novel representatives of bilaterian neuropeptide families and reconstruction of neuropeptide precursor evolution in ophiuroid echinoderms. Open Biol. 2017. https:\/\/doi.org\/10.1098\/rsob.170129.","journal-title":"Open Biol"},{"key":"2555_CR47","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00628","volume":"9","author":"NJ Wood","year":"2018","unstructured":"Wood NJ, Mattiello T, Rowe ML, Ward L, Perillo M, Arnone MI, et al. Neuropeptidergic systems in pluteus larvae of the sea urchin Strongylocentrotus purpuratus: neurochemical complexity in a \u201csimple\u201d nervous system. Front Endocrinol (Lausanne). 2018;9:628.","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2555_CR48","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.53370","author":"T Wang","year":"2020","unstructured":"Wang T, Cao Z, Shen Z, Yang J, Chen X, Yang Z, et al. Existence and functions of a kisspeptin neuropeptide signaling system in a non-chordate deuterostome species. Elife. 2020. https:\/\/doi.org\/10.7554\/eLife.53370.","journal-title":"Elife"},{"key":"2555_CR49","doi-asserted-by":"publisher","DOI":"10.3390\/ani13040705","author":"X Guo","year":"2023","unstructured":"Guo X, Zhang L, Xiao K. Effect of kisspeptin-type neuropeptide on locomotor behavior and muscle physiology in the sea cucumber Apostichopus japonicus. Animals. 2023. https:\/\/doi.org\/10.3390\/ani13040705.","journal-title":"Animals"},{"key":"2555_CR50","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.107974","volume":"231","author":"AD Hudson","year":"2022","unstructured":"Hudson AD, Kauffman AS. Metabolic actions of kisspeptin signaling: effects on body weight, energy expenditure, and feeding. Pharmacol Ther. 2022;231:107974.","journal-title":"Pharmacol Ther"},{"key":"2555_CR51","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.peptides.2018.12.003","volume":"112","author":"R Saito","year":"2019","unstructured":"Saito R, Tanaka K, Nishimura H, Nishimura K, Sonoda S, Ueno H, et al. Centrally administered kisspeptin suppresses feeding via nesfatin-1 and oxytocin in male rats. Peptides. 2019;112:114\u201324.","journal-title":"Peptides"},{"key":"2555_CR52","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.ygcen.2014.02.012","volume":"205","author":"MR Elphick","year":"2014","unstructured":"Elphick MR. SALMFamide salmagundi: the biology of a neuropeptide family in echinoderms. Gen Comp Endocrinol. 2014;205:23\u201335.","journal-title":"Gen Comp Endocrinol"},{"issue":"1","key":"2555_CR53","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-022-00953-y","volume":"20","author":"K-L Hu","year":"2022","unstructured":"Hu K-L, Chen Z, Li X, Cai E, Yang H, Chen Y, et al. Advances in clinical applications of kisspeptin-GnRH pathway in female reproduction. Reprod Biol Endocrinol. 2022;20(1):81.","journal-title":"Reprod Biol Endocrinol"},{"key":"2555_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2021.100977","volume":"65","author":"V Sobrino","year":"2022","unstructured":"Sobrino V, Avenda\u00f1o MS, Perdices-L\u00f3pez C, Jimenez-Puyer M, Tena-Sempere M. Kisspeptins and the neuroendocrine control of reproduction: recent progress and new frontiers in kisspeptin research. Front Neuroendocrinol. 2022;65:100977.","journal-title":"Front Neuroendocrinol"},{"issue":"1307","key":"2555_CR55","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1098\/rspb.1991.0020","volume":"243","author":"MR Elphick","year":"1991","unstructured":"Elphick MR, Price DA, Lee TD, Thorndyke MC. The SALMFamides: a new family of neuropeptides isolated from an echinoderm. Proc Biol Sci. 1991;243(1307):121\u20137.","journal-title":"Proc Biol Sci"},{"issue":"Pt 5","key":"2555_CR56","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1242\/jeb.00197","volume":"206","author":"R Melarange","year":"2003","unstructured":"Melarange R, Elphick MR. Comparative analysis of nitric oxide and SALMFamide neuropeptides as general muscle relaxants in starfish. J Exp Biol. 2003;206(Pt 5):893\u20139.","journal-title":"J Exp Biol"},{"issue":"2","key":"2555_CR57","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/0742-8413(94)00094-Q","volume":"110","author":"L D\u00edaz-Miranda","year":"1995","unstructured":"D\u00edaz-Miranda L, Garc\u00eda-Arrar\u00e1s JE. Pharmacological action of the heptapeptide GFSKLYFamide in the muscle of the sea cucumber Holothuria glaberrima (Echinodermata). Comp Biochem Physiol C Pharmacol Toxicol Endocrinol. 1995;110(2):171\u20136.","journal-title":"Comp Biochem Physiol C Pharmacol Toxicol Endocrinol"},{"issue":"Pt 22","key":"2555_CR58","doi-asserted-by":"publisher","first-page":"4273","DOI":"10.1242\/jeb.01910","volume":"208","author":"MR Elphick","year":"2005","unstructured":"Elphick MR, Thorndyke MC. Molecular characterisation of SALMFamide neuropeptides in sea urchins. J Exp Biol. 2005;208(Pt 22):4273\u201382.","journal-title":"J Exp Biol"},{"issue":"3","key":"2555_CR59","doi-asserted-by":"publisher","first-page":"260","DOI":"10.2307\/1543096","volume":"194","author":"MR Elphick","year":"1998","unstructured":"Elphick MR, Melarange R. Nitric oxide function in an echinoderm. Biol Bull. 1998;194(3):260\u20136.","journal-title":"Biol Bull"},{"issue":"2","key":"2555_CR60","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1037\/h0070051","volume":"2","author":"W Hamilton","year":"1922","unstructured":"Hamilton W. Co\u00f6rdination in the Starfish. III. The righting reaction as a phase of locomotion (righting and locomotion). J Comp Psychol. 1922;2(2):81.","journal-title":"J Comp Psychol"},{"issue":"1","key":"2555_CR61","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-25606-2","volume":"8","author":"LA Ya\u00f1ez-Guerra","year":"2018","unstructured":"Ya\u00f1ez-Guerra LA, Delroisse J, Barreiro-Iglesias A, Slade SE, Scrivens JH, Elphick MR. Discovery and functional characterisation of a luqin-type neuropeptide signalling system in a deuterostome. Sci Rep. 2018;8(1):7220.","journal-title":"Sci Rep"},{"issue":"542","key":"2555_CR62","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1098\/rstb.1937.0002","volume":"227","author":"JE Smith","year":"1937","unstructured":"Smith JE. On the nervous system of the starfish Mathasterias glacialis (L.). Philos Trans R Soc Lond B Biol Sci. 1937;227(542):111\u201373.","journal-title":"Philos Trans R Soc Lond B Biol Sci"}],"container-title":["BMC Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12915-026-02555-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12915-026-02555-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12915-026-02555-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T12:02:28Z","timestamp":1774526548000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12915-026-02555-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":62,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2555"],"URL":"https:\/\/doi.org\/10.1186\/s12915-026-02555-1","relation":{},"ISSN":["1741-7007"],"issn-type":[{"value":"1741-7007","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]},"assertion":[{"value":"7 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Experimental research on the starfish\n                      Asterias rubens\n                      was approved by the Queen Mary University of London Animal Welfare and Ethical Review Body (AWERB).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"74"}}