A 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. M Chabanon, MF Garcia-Parajo and F Campelo acknowledge support from the Government of Spain (FIS2015-63550-R, FIS2017-89560-R, BFU2015-73288-JIN, RYC-2017–22227, and PID2019-106232RB-I00/10.13039/501100011033; Severo Ochoa CEX2019-000910-S), Fundació Cellex, Fundació Mir-Puig, and Generalitat de Catalunya (CERCA, AGAUR), ERC Advanced Grant NANO-MEMEC (GA 788546) and LaserLab 4 Europe (GA 654148). I Raote and V Malhotra acknowledge funding by grants from the Ministerio de Economía, Industria y Competitividad Plan Nacional (BFU2013-44188-P) and Consolider (CSD2009-00016); support of the Spanish Ministry of Economy and Competitiveness, through the Programmes ‘Centro de Excelencia Severo Ochoa 2013–2017’ (SEV-2012–0208) and Maria de Maeztu Units of Excellence in R and D (MDM-2015–0502); and support of the CERCA Programme/Generalitat de Catalunya. I Raote, MF Garcia-Parajo, V Malhotra., and F Campelo acknowledge initial support by a BIST Ignite Grant (eTANGO). I Raote acknowledges support from the Spanish Ministry of Science, Innovation and Universities (IJCI-2017–34751). M Arroyo and N Walani acknowledge the support of the European Research Council (CoG-681434), and M Arroyo that of the Generalitat de Catalunya (2017-SGR-1278 and ICREA Academia prize for excellence in research) and of the Spanish Ministry of Economy and Competitiveness, through the Severo Ochoa Programme (CEX2018-000797- S)