biostudies-literatureRaote IGeneralitat de CatalunyaICREAEuropean Research CouncilFundacio Privada CellexSpanish Ministry of Science and InnovationBISTState Research AgencyGovernment of SpainMaría de Maeztu Unit of ExcellenceMinisterio de Economía y CompetitividadFundacio Privada Mir-PuigSpanish Governmente59426https://www.ebi.ac.uk/biostudies/studies/S-EPMC7704110biostudies-literatureUnknown9The endoplasmic reticulum (ER)-resident protein TANGO1 assembles into a ring around ER exit sites (ERES), and links procollagens in the ER lumen to COPII machinery, tethers, and ER-Golgi intermediate compartment (ERGIC) in the cytoplasm (Raote et al., 2018). Here, we present a theoretical approach to investigate the physical mechanisms of TANGO1 ring assembly and how COPII polymerization, membrane tension, and force facilitate the formation of a transport intermediate for procollagen export. Our results indicate that a TANGO1 ring, by acting as a linactant, stabilizes the open neck of a nascent COPII bud. Elongation of such a bud into a transport intermediate commensurate with bulky procollagens is then facilitated by two complementary mechanisms: (i) by relieving membrane tension, possibly by TANGO1-mediated fusion of retrograde ERGIC membranes and (ii) by force application. Altogether, our theoretical approach identifies key biophysical events in TANGO1-driven procollagen export.eLifeA physical mechanism of TANGO1-mediated bulky cargo export.PMC7704110ERC Advanced Grant (GA 788546)Ignite grant eTANGOBFU2013-44188-PConsolider CSD2009-00016Severo Ochoa Program CEX2018-000797- S654148LaserLab 4 Europe GA 654148ICREA academia788546CERCA programFIS2015-63550-RIJCI-2017-347512017-SGR-1278BFU2015-73288-JINFIS2017-89560-RSevero Ochoa Program SEV-2012–0208MDM-2015–0502681434RYC-2017-22227PID2019-106232RB-I00/ 10.13039/501100011033CoG-681434"Severo Ochoa" Programme (CEX2019-000910-S)Severo Ochoa Program SEV-2012-0208Maria de Maeztu MDM-2015-0502Walani NArroyo MGarcia-Parajo MFMalhotra VRaote IChabanon MCampelo FfalseA physical mechanism of TANGO1-mediated bulky cargo export.The endoplasmic reticulum (ER)-resident protein TANGO1 assembles into a ring around ER exit sites (ERES), and links procollagens in the ER lumen to COPII machinery, tethers, and ER-Golgi intermediate compartment (ERGIC) in the cytoplasm (Raote et al., 2018). Here, we present a theoretical approach to investigate the physical mechanisms of TANGO1 ring assembly and how COPII polymerization, membrane tension, and force facilitate the formation of a transport intermediate for procollagen export. Our results indicate that a TANGO1 ring, by acting as a linactant, stabilizes the open neck of a nascent COPII bud. Elongation of such a bud into a transport intermediate commensurate with bulky procollagens is then facilitated by two complementary mechanisms: (i) by relieving membrane tension, possibly by TANGO1-mediated fusion of retrograde ERGIC membranes and (ii) by force application. Altogether, our theoretical approach identifies key biophysical events in TANGO1-driven procollagen export.2020-01-01T00:00:00Z2020 Nov2025-04-05T12:54:41.19Z2025-04-05T12:54:41.19ZS-EPMC77041103316966710.7554/eLife.59426