{"paper_id":"2fcc9b50-3a2b-40aa-8a8c-fa641a79b65e","body_text":"Evolutionary conservation and adaptability of neuropeptide function: insights from sulfakinin/cholecystokinin-type signaling in an echinoderm, the sea cucumber Apostichopus japonicus | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evolutionary conservation and adaptability of neuropeptide function: insights from sulfakinin/cholecystokinin-type signaling in an echinoderm, the sea cucumber Apostichopus japonicus Huachen Liu, Hongliang Yang, Xiang Tian, Maurice Elphick, Chen Muyan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9103845/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background: Food ingestion is fundamental for animal survival and growth, with the cessation of feeding upon nutrient fulfillment being tightly regulated by a variety of satiety factors. Notably, sulfakinin/cholecystokinin (SK/CCK)-type neuropeptide signaling has been identified as an inhibitory regulator of food intake across the animal kingdom. However, its regulatory mechanism in feeding in deuterostome invertebrates remains unclear. Here, we characterized SK/CCK-type signaling in a deuterostome invertebrate, the sea cucumber Apostichopus japonicus (phylum Echinodermata). Results: A single SK/CCK-type precursor in A. japonicus generates two mature peptides (AjSK/CCK1, AjSK/CCK2) that activate a shared receptor (AjSK/CCKR), triggering Ca 2+ mobilization via the Gαq-dependent pathway and extracellular signal regulated kinase 1/2 (ERK1/2) phosphorylation. Both peptides induce dose-dependent contraction of longitudinal muscles, while AjSK/CCK2 additionally elicits sustained contraction of the posterior intestine, an effect absent in other gut regions. Long-term injection of both peptides reduces food intake and significantly downregulates orexin-type neuropeptide genes ( AjOrexin1P , AjOrexin2P ) in the circumoral nerve ring (CNR) and intestine. Conclusion: Unlike mammals, where CCK inhibits feeding by contracting the pyloric sphincter to delay gastric emptying, SK/CCK-type peptides in sea cucumbers exert their anorexic effect in part by selectively contracting the posterior intestine, thereby inhibiting intestinal emptying. This divergence in action sites highlights the evolutionary adaptability of SK/CCK-type signaling as a conserved inhibitory regulator of feeding across bilaterian animals. Elucidating these mechanisms in the economically important A. japonicus may inform development of appetite-promoting agents for sustainable aquaculture. Sulfakinin/cholecystokinin Feeding inhibition Intestinal contraction Evolutionary adaptability Echinoderm Full Text Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 08 Apr, 2026 Reviews received at journal 02 Apr, 2026 Reviews received at journal 27 Mar, 2026 Reviewers agreed at journal 18 Mar, 2026 Reviewers agreed at journal 18 Mar, 2026 Reviewers agreed at journal 18 Mar, 2026 Reviewers invited by journal 18 Mar, 2026 Editor assigned by journal 13 Mar, 2026 Submission checks completed at journal 13 Mar, 2026 First submitted to journal 12 Mar, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-9103845\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":608412252,\"identity\":\"b2910cec-5299-4be7-b5df-a21eb8bb9359\",\"order_by\":0,\"name\":\"Huachen Liu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Ocean University of China\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Huachen\",\"middleName\":\"\",\"lastName\":\"Liu\",\"suffix\":\"\"},{\"id\":608412253,\"identity\":\"58f22d22-3a81-461b-883b-3d6684b7fd6b\",\"order_by\":1,\"name\":\"Hongliang 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Apostichopus japonicus\",\"fulltext\":[],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":false,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":true,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":true,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"bmc-biology\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":false,\"externalIdentity\":\"\",\"sideBox\":\"Learn more about [BMC Biology](https://bmcbiol.biomedcentral.com/)\",\"snPcode\":\"12915\",\"submissionUrl\":\"https://submission.springernature.com/new-submission/12915/3\",\"title\":\"BMC 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Notably, sulfakinin/cholecystokinin (SK/CCK)-type neuropeptide signaling has been identified as an inhibitory regulator of food intake across the animal kingdom. However, its regulatory mechanism in feeding in deuterostome invertebrates remains unclear. Here, we characterized SK/CCK-type signaling in a deuterostome invertebrate, the sea cucumber \\u003cem\\u003eApostichopus japonicus\\u003c/em\\u003e (phylum Echinodermata).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults: \\u003c/strong\\u003eA single SK/CCK-type precursor in \\u003cem\\u003eA. japonicus\\u003c/em\\u003e generates two mature peptides (AjSK/CCK1, AjSK/CCK2) that activate a shared receptor (AjSK/CCKR), triggering Ca\\u003csup\\u003e2+\\u003c/sup\\u003e mobilization via the Gαq-dependent pathway and extracellular signal regulated kinase 1/2 (ERK1/2) phosphorylation. Both peptides induce dose-dependent contraction of longitudinal muscles, while AjSK/CCK2 additionally elicits sustained contraction of the posterior intestine, an effect absent in other gut regions. Long-term injection of both peptides reduces food intake and significantly downregulates orexin-type neuropeptide genes (\\u003cem\\u003eAjOrexin1P\\u003c/em\\u003e, \\u003cem\\u003eAjOrexin2P\\u003c/em\\u003e) in the circumoral nerve ring (CNR) and intestine.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusion: \\u003c/strong\\u003eUnlike mammals, where CCK inhibits feeding by contracting the pyloric sphincter to delay gastric emptying, SK/CCK-type peptides in sea cucumbers exert their anorexic effect in part by selectively contracting the posterior intestine, thereby inhibiting intestinal emptying. This divergence in action sites highlights the evolutionary adaptability of SK/CCK-type signaling as a conserved inhibitory regulator of feeding across bilaterian animals. 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