A physical mechanism of TANGO1-mediated bulky cargo export

ABSTRACT The endoplasmic reticulum (ER)-resident transmembrane protein TANGO1 assembles into a ring around COPII subunits at ER exit sites (ERES), and links cytosolic membrane-remodeling machinery, tethers, and ER-Golgi intermediate compartment (ERGIC) membranes to procollagens in the ER lumen (Raote et al ., 2018). This arrangement is proposed to create a route for direct transfer of procollagens from ERES to ERGIC membranes via a tunnel. Here, we present a physical model in which TANGO1 forms a linear filament that wraps around COPII lattices at ERES to stabilize the neck of a growing transport intermediate. Importantly, our results show that TANGO1 is able to stabilize ERES-ERGIC opening by regulating ER membrane tension to allow procollagen loading and export from the ER. Altogether, our theoretical approach provides a mechanical framework of TANGO1 as a membrane tension regulator to control procollagen export from the ER.