Abstract
Tango1 helps the efficient delivery of large proteins to the cell surface. We show here that loss of Tango1, in addition to interfering with protein secretion, causes ER stress and defects in cell and ER/Golgi morphology. We find that the previously observed dependence of smaller cargos on Tango1 is a secondary effect, due to an indirect requirement: if large cargos like Dumpy, which we identify here as a new Tango1 cargo, are removed from the cell, non-bulky proteins re-enter the secretory pathway. Removal of the blocking cargo also attenuates the ER-stress response, and cell morphology is restored. Thus, failures in the secretion of non-bulky proteins, ER stress and defective cell morphology are secondary consequences of the retention of cargo. By contrast, the ERES defects in Tango1-depleted cells persist in the absence of bulky cargo, showing that they are due to a secretion-independent function of Tango1. Therefore, the maintenance of proper ERES architecture may be a primary function for Tango1.
