Calcium-binding protein CALU-1 is essential for proper collagen formation in Caenorhabditis elegans

Calcium-binding protein CALU-1 is essential for proper collagen formation in Caenorhabditis elegans | 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 Calcium-binding protein CALU-1 is essential for proper collagen formation in Caenorhabditis elegans Kyung Eun Lee, Jeong Hoon Cho, Hyun-Ok Song This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5192418/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 25 Jan, 2025 Read the published version in Cellular and Molecular Life Sciences → Version 1 posted 5 You are reading this latest preprint version Abstract Collagen, a major component of the extracellular matrix, is crucial for the structural integrity of the Caenorhabditis elegans cuticle. While several proteins involved in collagen biosynthesis have been identified, the complete regulatory network remains unclear. This study investigates the role of CALU-1, an ER-resident calcium-binding protein, in cuticle collagen formation and maintenance. We employed genetic analyses, including the generation of single and double mutants, scanning electron microscopy, and transcriptome profiling to characterize CALU-1 function. Our results demonstrate that CALU-1 is essential for proper cuticle structure, including annuli, furrows, and alae formation. Synthetic lethality was observed between calu-1 and dpy-18 (encoding a prolyl 4-hydroxylase subunit) mutations, while double mutants of calu-1 with peptidyl-prolyl cis-trans isomerase (PPIase) genes exhibited exacerbated phenotypes. CALU-1 deficiency led to altered collagen stability, increased cuticle permeability, and differential expression of stress response genes similar to collagen mutants. We conclude that CALU-1 plays a critical role in regulating collagen biosynthesis, possibly by modulating the ER environment to optimize the function of collagen-modifying enzymes. These findings provide new insights into the complex regulation of extracellular matrix formation in C. elegans , with potential implications for understanding related processes in other organisms. Nematode exoskeleton extracelluar matrix calumenin cuticle permeability stress Full Text Cite Share Download PDF Status: Published Journal Publication published 25 Jan, 2025 Read the published version in Cellular and Molecular Life Sciences → Version 1 posted Editorial decision: Accept as is 05 Jan, 2025 Reviewers agreed at journal 10 Dec, 2024 Reviewers invited by journal 09 Dec, 2024 Editor assigned by journal 02 Dec, 2024 First submitted to journal 29 Nov, 2024 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-5192418","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":388293911,"identity":"7363f593-c3a2-40f7-88b9-f4409daca6d9","order_by":0,"name":"Kyung Eun Lee","email":"","orcid":"","institution":"Wonkwang University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kyung","middleName":"Eun","lastName":"Lee","suffix":""},{"id":388293912,"identity":"f95f4bee-bd6b-486f-9f73-c3ac6e140450","order_by":1,"name":"Jeong Hoon Cho","email":"","orcid":"","institution":"Chosun University","correspondingAuthor":false,"prefix":"","firstName":"Jeong","middleName":"Hoon","lastName":"Cho","suffix":""},{"id":388293913,"identity":"6623ce71-a7b5-4858-a93a-7e13a4c0dede","order_by":2,"name":"Hyun-Ok Song","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuUlEQVRIiWNgGAWjYBACAwhlwyABYSQQrSWNdC2HSdBizt7+8HHBr/OJM2ckMH74wZCWT1CLZc8ZY+OZfbcTZ0skMEv2MORYNhB02I0cNmnentu58yQSGKQZGCoMCNpicCP9GVDLOZAW5t9Eakkwk+b5cSAX6DA2oC05RGg5A/QLb0Ny/cyeh22WPQZpRGg5Dgwxnj92xhLHkw/f+FGRTFgLGDC2gckGeDQRAf4QrXIUjIJRMApGIgAAa505lm+RN4gAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-7953-3384","institution":"Wonkwang University College of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Hyun-Ok","middleName":"","lastName":"Song","suffix":""}],"badges":[],"createdAt":"2024-10-02 10:53:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5192418/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5192418/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00018-025-05582-3","type":"published","date":"2025-01-25T15:58:01+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":74859262,"identity":"1128e3e4-0276-4385-a372-a67fcb1e2fca","added_by":"auto","created_at":"2025-01-27 16:14:01","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":4090582,"visible":true,"origin":"","legend":"","description":"","filename":"LeeetalCMLSCleanver..pdf","url":"https://assets-eu.researchsquare.com/files/rs-5192418/v1_covered_4780bc5b-e205-4d99-ba7c-c4ca7d2d8ec4.pdf"}],"financialInterests":"","formattedTitle":"Calcium-binding protein CALU-1 is essential for proper collagen formation in Caenorhabditis elegans","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"cellular-and-molecular-life-sciences","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"life","sideBox":"Learn more about [Cellular and Molecular Life Sciences](https://link.springer.com/journal/18)","snPcode":"18","submissionUrl":"https://www.editorialmanager.com/life/default2.aspx","title":"Cellular and Molecular Life Sciences","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Nematode, exoskeleton, extracelluar matrix, calumenin, cuticle permeability, stress","lastPublishedDoi":"10.21203/rs.3.rs-5192418/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5192418/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCollagen, a major component of the extracellular matrix, is crucial for the structural integrity of the \u003cem\u003eCaenorhabditis elegans\u003c/em\u003e cuticle. While several proteins involved in collagen biosynthesis have been identified, the complete regulatory network remains unclear. This study investigates the role of CALU-1, an ER-resident calcium-binding protein, in cuticle collagen formation and maintenance. We employed genetic analyses, including the generation of single and double mutants, scanning electron microscopy, and transcriptome profiling to characterize CALU-1 function. Our results demonstrate that CALU-1 is essential for proper cuticle structure, including annuli, furrows, and alae formation. Synthetic lethality was observed between \u003cem\u003ecalu-1\u003c/em\u003e and \u003cem\u003edpy-18\u003c/em\u003e (encoding a prolyl 4-hydroxylase subunit) mutations, while double mutants of \u003cem\u003ecalu-1\u003c/em\u003e with peptidyl-prolyl cis-trans isomerase (PPIase) genes exhibited exacerbated phenotypes. 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