Endoplasmic reticulum exit sites are segregated for secretion based on cargo size

Saxena, Sonashree; Foresti, Ombretta; Liu, Aofei; Androulaki, Stefania; Rodriguez, Maria Pena; Raote, Ishier; Aridor, Meir; Cui, Bianxiao; Malhotra, Vivek

Endoplasmic reticulum exit sites are segregated for secretion based on cargo size

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dc.contributor.author Saxena, Sonashree
dc.contributor.author Foresti, Ombretta
dc.contributor.author Liu, Aofei
dc.contributor.author Androulaki, Stefania
dc.contributor.author Rodriguez, Maria Pena
dc.contributor.author Raote, Ishier
dc.contributor.author Aridor, Meir
dc.contributor.author Cui, Bianxiao
dc.contributor.author Malhotra, Vivek
dc.date.accessioned 2025-02-04T12:58:21Z
dc.date.embargoEnd info:eu-repo/date/embargoEnd/2025-07-10
dc.date.issued 2024
dc.description.abstract TANGO1, TANGO1-Short, and cTAGE5 form stable complexes at the endoplasmic reticulum exit sites (ERES) to preferably export bulky cargoes. Their C-terminal proline-rich domain (PRD) binds Sec23A and affects COPII assembly. The PRD in TANGO1-Short was replaced with light-responsive domains to control its binding to Sec23A in U2OS cells (human osteosarcoma). TANGO1-ShortΔPRD was dispersed in the ER membrane but relocated rapidly, reversibly, to pre-existing ERES by binding to Sec23A upon light activation. Prolonged binding between the two, concentrated ERES in the juxtanuclear region, blocked cargo export and relocated ERGIC53 into the ER, minimally impacting the Golgi complex organization. Bulky collagen VII and endogenous collagen I were collected at less than 47% of the stalled ERES, whereas small cargo molecules were retained uniformly at almost all the ERES. We suggest that ERES are segregated to handle cargoes based on their size, permitting cells to traffic them simultaneously for optimal secretion.
dc.description.sponsorship We acknowledge the support of the Spanish Ministry of Science and Innovation through the Centro de Excelencia Severo Ochoa (CEX2020-001049-S, MCIN/AEI/10.13039/501100011033); the Generalitat de Catalunya through the CERCA programme and the EMBL partnership; Ministerio de Ciencia e Innovación (Ramon y Cajal Fellow, RYC-2016-20919) to O.F.;Ministerio de Economía y Competitividad: IJCI-2017-34751 and Fondation pour la Recherche Medicale (FRM), AJE202210016216 to I.R.; Ministerio de Economía y Competitividad:SEV-2012-0208, BFU2013-44188-P (funded by Agencia Estatal de Investigación [AEI]), and CSD2009-00016 (CONSOLIDER - INGENIO 2010) to V.M. The National Institutes of Health NIH (R35GM141598, (R01NS121934) and seed grant from the Stanford Wu Tsai Neuroscience Institute to B.C. and A.L. This project has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program under grant agreement no. 951146. This publication is part of the project TARTAFI (ref. PDC2021-121870-I00), funded by MCIN/AEI/10.13039/501100011033, by “ERDF A way of making Europe,” and by the “European Union NextGenerationEU/PRTR.”.
dc.embargo.liftdate 2025-07-10
dc.format.mimetype application/pdf
dc.identifier.citation Saxena S, Foresti O, Liu A, Androulaki S, Pena Rodriguez M, Raote I, et al. Endoplasmic reticulum exit sites are segregated for secretion based on cargo size. Dev Cell. 2024 Oct 7;59(19):2593-2608.e6. DOI: 10.1016/j.devcel.2024.06.009
dc.identifier.doi http://dx.doi.org/10.1016/j.devcel.2024.06.009
dc.identifier.issn 1534-5807
dc.identifier.uri http://hdl.handle.net/10230/69485
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Dev Cell. 2024 Oct 7;59(19):2593-2608.e6
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/951146
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/CEX2020-001049-S
dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/IJCI-2017-34751
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SEV-2012-0208
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2013-44188-P
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PE/PDC2021-121870-I00
dc.rights.accessRights info:eu-repo/semantics/embargoedAccess
dc.subject.keyword COPII
dc.subject.keyword ER export
dc.subject.keyword ERES
dc.subject.keyword TANGO1
dc.subject.keyword Collagens
dc.subject.keyword Endoplasmic reticulum
dc.subject.keyword Membrane traffic
dc.subject.keyword Optogenetics
dc.subject.keyword Protein secretion
dc.subject.keyword Secretory cargo
dc.title Endoplasmic reticulum exit sites are segregated for secretion based on cargo size
dc.type info:eu-repo/semantics/article
dc.type.version info:eu-repo/semantics/acceptedVersion

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