Glycophagy is an ancient bilaterian pathway supporting metabolic adaptation through STBD1 structural evolution

Glycophagy is an ancient bilaterian pathway supporting metabolic adaptation through STBD1 structural evolution | 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 Glycophagy is an ancient bilaterian pathway supporting metabolic adaptation through STBD1 structural evolution Shikai Liu, Liting Ren, Yitian Bai, Chenyu Shi, Qi Li, Daniel Macqueen This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6392273/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 20 Jan, 2026 Read the published version in Communications Biology → Version 1 posted You are reading this latest preprint version Abstract Glycophagy, a selective form of autophagy critical for glycogen homeostasis, relies on the glycogen cargo receptor called starch-binding domain-containing protein 1 (STBD1), yet its evolutionary origins remain elusive. Here, we provide evidence that the Pacific oyster Crassostrea gigas utilizes glycophagy to manage glycogen mobilization during periods of energy deprivation. We identify an oyster STBD1 protein, and trace its origins through phylogenetic and comparative genomic analysis of the carbohydrate binding module family 20 (CBM20) domain within this protein across 61 metazoan species. Oyster STBD1 and those in other invertebrates contain the N-terminal CBM20, contrasting the C-terminal location of CBM20 in vertebrate STBD1. N-terminal CBM20 STBD1 proteins have a deep origin in bilaterians, with the vertebrate structural arrangement arising at the chordate root. Structural modelling and functional studies reveal that the N-terminal organization of the CBM20 domain in STBD1 enhances glycogen binding, with subsequent anchoring by GABARAPL2, facilitating an increased glycogen flux into autophagosomes for lysosomal degradation. We conclude that glycophagy is deeply conserved in bilaterians and that STBD1 structural evolution underlies potentially adaptive variation in metabolic strategies across distinct animal clades. Biological sciences/Evolution/Molecular evolution Biological sciences/Physiology/Metabolism Glycophagy metabolism oyster protein evolution STBD1 Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryTablesCB.xlsx Supplementary Tables_CB SupplementaryDataCB.xlsx Supplementary Data_CB SupplementaryInformationCB.pdf Supplementary Information_CB Cite Share Download PDF Status: Published Journal Publication published 20 Jan, 2026 Read the published version in Communications Biology → 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. 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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-6392273","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":447339004,"identity":"19ca27ce-a16a-49dd-8beb-29f9d1d2d704","order_by":0,"name":"Shikai 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