Pericentrosomal redistribution of the endoplasmic reticulum ensures organelle symmetric inheritance and mitotic progression

Pericentrosomal redistribution of the endoplasmic reticulum ensures organelle symmetric inheritance and mitotic progression | 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 Biological Sciences - Article Pericentrosomal redistribution of the endoplasmic reticulum ensures organelle symmetric inheritance and mitotic progression Pengli Zheng, Xiangyu Xu, Yalin Liu, Rongyi Wang, Wenwen Xu, Hao Shi, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8115633/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Symmetric cell division entails the equal distribution of cellular components to daughter cells. However, the mechanisms governing organelle segregation remain elusive. The endoplasmic reticulum (ER), comprising pericentrosomal sheets and peripheral tubules in interphase, serves as a central hub for sensing cellular states and coordinating other organelle dynamics. Dysregulation of ER morphology and distribution is implicated in developmental disorders and tumorigenesis. Here, we show that upon mitotic entry, the ER undergoes reverse redistribution: tubular ER accumulates around the centrosomes, while sheet-like ER relocates to the periphery. Mechanistically, the tubular ER protein RTN4 is phosphorylated by CDK1 and translocated toward centrosomes in a dynein-dependent manner by binding to Rab11 GTPase, thereby promoting tubularization of the pericentrosomal ER. RTN4-mediated ER reorganization ensures symmetric distribution and inheritance of the ER, further contributing to the symmetric segregation of other organelles and proper mitotic progression. In Caenorhabditis elegans, the RTN4 homolog RET-1 also drives pericentrosomal ER enrichment during embryonic cell division and facilitates development. Thus, our study uncovers the mechanism of mitotic ER symmetry remodeling and its roles in organelle inheritance, mitotic progression, and development. Biological sciences/Cell biology/Organelles/Endoplasmic reticulum Biological sciences/Cell biology/Cell division/Mitosis Full Text Additional Declarations There is NO Competing Interest. Supplementary Files SupplementaryVideo1.mp4 Supplementary Video 1. RTN4B and pan-ER dynamics during mitosis SupplementaryVideo2.mp4 Supplementary Video 2. 3D reconstruction of pericentrosomal and peripheral ER from FIB-SEM data SupplementaryVideo3.mp4 Supplementary Video 3. Mitotic duration of knockout cells Cite Share Download PDF Status: Posted 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-8115633","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Biological Sciences - Article","associatedPublications":[],"authors":[{"id":556009027,"identity":"f6167d7f-c063-4cb2-b376-b0f6950b8bfa","order_by":0,"name":"Pengli Zheng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2ElEQVRIiWNgGAWjYDACCTBpIcfAA6LZiNciYUy6lsQGorXIz24+9vDrDon07TxnDBg+lB1m4J/dgF8L45xj6cayZyRyd/b2GDDOOHeYQeLOAfxamCVyzKQl2yRyN5znMWDmbTvMYCCRgF8Lm0T+N5CWdAOQlr/EaOGRyGGT/NgmkWBwtseAmZEYLRISaWbSjGckDHf2HCs42HMunUfiBgEt8jOSn0n+3GEjb86TvPHBjzJrOf4ZBLSAADNvAwODAZBxAORSwuqBgPEnVMsoGAWjYBSMAqwAANOyPShMs2wXAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-3797-4023","institution":"Peking University","correspondingAuthor":true,"prefix":"","firstName":"Pengli","middleName":"","lastName":"Zheng","suffix":""},{"id":556009028,"identity":"27606ecd-346a-4601-993e-e821e8225ea7","order_by":1,"name":"Xiangyu Xu","email":"","orcid":"","institution":"Peking University","correspondingAuthor":false,"prefix":"","firstName":"Xiangyu","middleName":"","lastName":"Xu","suffix":""},{"id":556009029,"identity":"fbc903f5-231d-4c2f-9086-36a59c247a25","order_by":2,"name":"Yalin Liu","email":"","orcid":"","institution":"Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yalin","middleName":"","lastName":"Liu","suffix":""},{"id":556009030,"identity":"1226d111-ae4b-457f-a1ae-2a12223bff63","order_by":3,"name":"Rongyi Wang","email":"","orcid":"","institution":"Peking University","correspondingAuthor":false,"prefix":"","firstName":"Rongyi","middleName":"","lastName":"Wang","suffix":""},{"id":556009031,"identity":"c73e345e-6d11-428e-aaab-0608748d5348","order_by":4,"name":"Wenwen Xu","email":"","orcid":"","institution":"Peking University","correspondingAuthor":false,"prefix":"","firstName":"Wenwen","middleName":"","lastName":"Xu","suffix":""},{"id":556009032,"identity":"2d4d1c11-3174-4a4d-bb91-d47be49a5d69","order_by":5,"name":"Hao Shi","email":"","orcid":"","institution":"Peking University","correspondingAuthor":false,"prefix":"","firstName":"Hao","middleName":"","lastName":"Shi","suffix":""},{"id":556009033,"identity":"1a787d28-d5be-40e0-a8c0-9a6b1daf0fb9","order_by":6,"name":"Ning Huang","email":"","orcid":"","institution":"Xi’an Jiaotong University","correspondingAuthor":false,"prefix":"","firstName":"Ning","middleName":"","lastName":"Huang","suffix":""},{"id":556009034,"identity":"db890e7e-4944-40d5-a719-55f1ff43feba","order_by":7,"name":"Junlin Teng","email":"","orcid":"https://orcid.org/0000-0002-7611-0631","institution":"Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education and State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University","correspondingAuthor":false,"prefix":"","firstName":"Junlin","middleName":"","lastName":"Teng","suffix":""},{"id":556009035,"identity":"45312077-2df9-44ff-943c-5698814639ee","order_by":8,"name":"Jin Meng","email":"","orcid":"","institution":"Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jin","middleName":"","lastName":"Meng","suffix":""},{"id":556009036,"identity":"8ff6ecc5-211c-40b4-9de4-fafb764c7566","order_by":9,"name":"Jianguo Chen","email":"","orcid":"","institution":"Peking University","correspondingAuthor":false,"prefix":"","firstName":"Jianguo","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2025-11-14 13:41:45","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8115633/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8115633/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":103505850,"identity":"32aa72c5-3f50-414b-8f3c-9b09ec503c72","added_by":"auto","created_at":"2026-02-26 13:33:14","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5854693,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8115633/v1_covered_b2022aad-ec7d-46fd-b1be-b400e123a6df.pdf"},{"id":97839499,"identity":"89c018fd-4148-49d1-a10b-6381f5431340","added_by":"auto","created_at":"2025-12-10 03:21:25","extension":"mp4","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":10572210,"visible":true,"origin":"","legend":"\u003cp\u003eSupplementary Video 1. 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