A physical mechanism of TANGO1-mediated bulky cargo export

Abstract

25The endoplasmic reticulum (ER)-resident transmembrane protein TANGO1 assembles 26 into rings around COPII subunits at ER exit sites (ERES), and links cytosolic membrane-27 remodeling machinery, tethers, and ER-Golgi intermediate compartment (ERGIC) mem-28 branes to procollagens in the ER lumen (Raote et al., 2018). This arrangement is proposed 29to create a direct route for transfer of procollagens from ERES to ERGIC membranes. 30Here, we present a physical model in which TANGO1 forms a linear filament that wraps 31around COPII lattices at ERES to stabilize the neck of a growing carrier on the cytoplas-32 mic face of the ER. Importantly, our results show that TANGO1 can induce the formation 33 of transport intermediates by regulating ER membrane tension. Altogether, our theoret-34ical approach provides a mechanical framework of how TANGO1 acts as a membrane 35 tension regulator to control procollagen export from the ER. 36 95 mation model. ERES consisting of COPII subunits assemble into in-plane circular lattices (orange), 96whereas proteins of the TANGO1 family assemble into filaments by lateral protein-protein interactions 97 (light blue). A tug-of-war between the affinity of the TANGO1 filament to bind COPII subunits (promoting 98 wetting) and the resistance of the filament to be bent (promoting dewetting) controls the wetting-dewetting 99 transition. Only when TANGO1 wets the COPII lattice, it acts as a linactant by stabilizing the peripheral 100 COPII subunits. 101 102 5

On Gaussian Curvature and Membrane Fission

“…This is done by a phase-field methodology, which has been used to study a variety of systems based on the Helfrich theory for cellular membranes [25][26][27][28][29][30][31][32][33][34] . Numerical integration results show that without the inclusion of the Gaussian curvature the system exhibits a pearling instability, which has been already observed in many simulations 26,35,36 and experiments 37,38 . Pearling happens in membranes due to the spontaneous curvature, and the Gaussian curvature may lead to the fission of the pearls.…”

A general role for TANGO1, encoded by MIA3, in secretory pathway organization and function

“…TANGO1, encoded by Mia3, was identified in a genetic screen in Drosophila S2 cells, as a factor required for the secretion of a horseradish peroxidase reporter (Bard et al, 2006). Considerable data have since implicated this as a selective cargo receptor for procollagens (Maeda et al, 2016;Raote et al, 2020;Raote et al, 2018;Saito et al, 2011;Santos et al, 2015) and other large cargo proteins such as apolipoproteins (Santos et al, 2016). Knockout of TANGO1 in Drosophila leads to defects in ER morphology, induction of ER stress, and defects in cargo secretion (Rios-Barrera et al, 2017).…”

A general role for MIA3/TANGO1 in secretory pathway organization and function

“…TANGO1, encoded by Mia3, was identified in a genetic screen in Drosophila S2 cells, as a factor required for the secretion of a horseradish peroxidase reporter (Bard et al, 2006). Considerable data have since implicated this as a selective cargo receptor for procollagens (Maeda et al, 2016;Raote et al, 2020;Raote et al, 2018;Saito et al, 2011;Santos et al, 2015) and other large cargo proteins such as apolipoproteins (Santos et al, 2016). Knockout of TANGO1 in Drosophila leads to defects in ER morphology, induction of ER stress, and defects in cargo secretion (Rios-Barrera et al, 2017).…”