Fig. 8.

Model depicting the organization of the early secretory pathway in the presence and absence of TFG. Initiation of COPII carrier formation occurs at ER subdomains harboring Sec16A and Tango1-like cargo receptors, which interact directly with Sec23. Full assembly of the outer COPII cage interferes with these interactions and facilitates the release of the transport carrier into the ER/ERGIC interface, where TFG competes with Sec31 for Sec23 binding. The outer coat is ultimately displaced by TFG, which clusters inner COPII-coated transport carriers until they tether and fuse with adjacent ERGIC membranes. In the absence of TFG, transport carriers harboring both the inner and outer layers of the COPII coat continue to form but diffuse away from the ER/ERGIC interface, slowing secretory transport of conventional COPII-dependent cargoes.