Cargo control of bulky carrier formation during collagen export.

Abstract

Procollagen, is exported from the endoplasmic reticulum (ER) in the form of rigid 300 nm long triple-helical structures. Surprisingly, the export machinery for procollagen relies on COPII components, which typically form lipid vesicle carriers of about 80 nm, much smaller than procollagen cargos. Recently the ER-resident protein TANGO1 has been shown to organize into rings around COPII coats at ER exit sites (ERES), suggesting it plays a key role in the formation of large carriers. Here we propose a continuum biophysical model to study the dynamic interplay between the ER membrane, procollagen, COPII, and TANGO1 during the formation of a bulky carrier. Our model couples Helfrich bending energy of lipid membranes to the thermodynamic contribution of two interacting membrane-bound species, namely COPII and TANGO1. Our results show that TANGO1 stabilizes incomplete buds by self-organizing into rings around COPII domains, as observed experimentally. We then tested different mechanisms hypothesized to contribute to the formation of bulky carriers compatible with procollagen export, and showed that their coordinated action facilitates the formation of carriers. Our findings suggests that TANGO1 not only serves as a mechanical element of ER export sites, but might also play an important coordinating role in the genesis of procollagen carriers.