A physical mechanism of TANGO1-mediated bulky cargo export

Raote, Ishier; Chabanon, Morgan; Walani, Nikhil; Arroyo, Marino; Garcia-Parajo, Maria F.; Malhotra, Vivek; Campelo, Felix

doi:http://dx.doi.org/10.7554/eLife.59426

A physical mechanism of TANGO1-mediated bulky cargo export

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Raote I, Chabanon M,Walani N, Arroyo M, Garcia-Parajo MF, Malhotra M et al. A physical mechanism of TANGO1-mediated bulky cargo export. Elife. 2020 Nov 10;9:e59426. DOI: 10.7554/eLife.59426

Abstract

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.