Remodeling of extracellular matrix collagen IV by MIG-6/papilin regulates neuronal architecture

Remodeling of extracellular matrix collagen IV by MIG-6/papilin regulates neuronal architecture | 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 Article Remodeling of extracellular matrix collagen IV by MIG-6/papilin regulates neuronal architecture Claire Bénard, Malika Nadour, Robert VALETTE REVENO LEATIS, Marie BIARD, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5962240/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted You are reading this latest preprint version Abstract Neuronal architecture established embryonically must persist lifelong to ensure normal brain function. However, little is understood about the mechanisms behind the long-term maintenance of neuronal organization. To uncover maintenance mechanisms, we performed a suppressor screen in sax-7/L1CAM mutants, which exhibit progressive disorganization with age. We identified the conserved extracellular matrix protein MIG-6/papilin as a key regulator of neuronal maintenance. Combining incisive molecular genetics, structural predictions, in vivo quantitative imaging, and cutting-edge Brillouin microscopy, we show that MIG-6/papilin remodels extracellular matrix collagen IV, working in concert with the secreted enzymes MIG-17/ADAMTS and PXN-2/peroxidasin. This remodeling impacts tissue biomechanics and ensures neuronal stability, even under increased mechanical stress. Our findings highlight an extracellular mechanism by which MIG-6/papilin supports the integrity of neuronal architecture throughout life. This work provides critical insights into the molecular basis of sustaining neuronal architecture and offers a foundation for understanding age-related and neurodegenerative disorders. Biological sciences/Developmental biology/Experimental organisms/Model invertebrates/Caenorhabditis elegans Biological sciences/Genetics/Development Biological sciences/Neuroscience/Genetics of the nervous system Biological sciences/Neuroscience/Neural ageing Papilin MIG-6 collagen IV extracellular matrix neuronal maintenance Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SourcedataFIGURESNadouretal.xlsx Source data FIGURES Nadour et al SourcedataSUPPLEMENTARYFIGURESNadouretal.xlsx Source data SUPPLEMENTARY FIGURES Nadour et al mig6qv33qyIs46mutantanimalWHOLEHEAD.avi Collagen IV fibrotic structures in mig-6(qv33) mutants (whole head) mig6qv33qyIs46mutantanimalTERMINALBULBregion.avi Collagen IV fibrotic structures in mig-6(qv33) mutants (zoomed) WildtypeqyIs46animalTERMINALBULBregion.avi Normal collagen IV in the wild type Cite Share Download PDF Status: Under Review Version 1 posted 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-5962240","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":411970204,"identity":"38ae0e34-5bec-48b2-aae0-b6ec895b1ed0","order_by":0,"name":"Claire Bénard","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYBACAzDJxsDAx8DYwMBQQYoWNrCWM6RpAQLGNiK0mLP3HvxcUcYgz8Z+uO3Dx3mHZfunHWD88AOPFsuec8mSZ84xGLbxJDbPnLntsPGM2wnMkj34HHYjx0CysY0hgY0hsZmZd9vhxIbbQDYPPi333xj/BGvhf9jM/HfO4cT5QC2Mf/DawmMGsUUCaAtjw+HEDUAtzPhssezJMbNsOCdh2CbxsJmx51i68cbbic3SMni0mLOfMb7ZUGYjz8+f/pjhR4217LzbyQc/vsGjBQok4CxghILilBRAqvpRMApGwSgYAQAAH9pLnI6TXFIAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0002-1919-1877","institution":"Université du Québec à Montréal","correspondingAuthor":true,"prefix":"","firstName":"Claire","middleName":"","lastName":"Bénard","suffix":""},{"id":411970205,"identity":"deddb7a9-e35e-4c4d-816c-3824a9591aaf","order_by":1,"name":"Malika Nadour","email":"","orcid":"","institution":"Université du Québec à Montréal","correspondingAuthor":false,"prefix":"","firstName":"Malika","middleName":"","lastName":"Nadour","suffix":""},{"id":411970206,"identity":"fc648c14-6374-4666-b52c-bd043a17e4f3","order_by":2,"name":"Robert VALETTE REVENO LEATIS","email":"","orcid":"","institution":"Université du Québec à Montréal","correspondingAuthor":false,"prefix":"","firstName":"Robert","middleName":"VALETTE REVENO","lastName":"LEATIS","suffix":""},{"id":411970207,"identity":"0cb95a9b-f356-44a8-a5cd-5057e972e84b","order_by":3,"name":"Marie BIARD","email":"","orcid":"","institution":"Université du Québec à Montréal","correspondingAuthor":false,"prefix":"","firstName":"Marie","middleName":"","lastName":"BIARD","suffix":""},{"id":411970208,"identity":"7fc5a3cf-0e9e-4bcb-b3da-533557015035","order_by":4,"name":"Noémie Frébault","email":"","orcid":"","institution":"Université Claude Bernard Lyon 1, CNRS UMR 5284, INSERM U1314","correspondingAuthor":false,"prefix":"","firstName":"Noémie","middleName":"","lastName":"Frébault","suffix":""},{"id":411970209,"identity":"04524a50-979b-4538-a11b-5c65e2233650","order_by":5,"name":"Lise Rivollet","email":"","orcid":"","institution":"Université du Québec à Montréal","correspondingAuthor":false,"prefix":"","firstName":"Lise","middleName":"","lastName":"Rivollet","suffix":""},{"id":411970210,"identity":"47cc268f-2154-403f-aad5-32972b1b849d","order_by":6,"name":"Philippe ST-LOUIS","email":"","orcid":"","institution":"Université du Québec à Montréal","correspondingAuthor":false,"prefix":"","firstName":"Philippe","middleName":"","lastName":"ST-LOUIS","suffix":""},{"id":411970211,"identity":"8d4be89f-8787-4265-a35a-2c4f5fbfb25f","order_by":7,"name":"Cassandra R. 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