TANGO1 marshals the early secretory pathway for cargo export

TANGO1 protein facilitates the endoplasmic reticulum (ER) export of large cargoes that cannot be accommodated in 60 nm transport vesicles. It assembles into a ring in the plane of the ER membrane to create a distinct domain. Its lumenal portion collects and sorts folded cargoes while its cytoplasmic domains collar COPII coats, recruit retrograde COPI-coated membranes that fuse within the TANGO1 ring, thus opening a tunnel for cargo transfer from the ER into a growing export conduit. This mode of cargo transfer bypasses the need for vesicular intermediates and is used to export the most abundant and bulky cargoes. The evolution of TANGO1 and its activities defines the difference between yeast and animal early secretory pathways.