The Golgi vesicle tether p115 can bind directly to the ER exit site organiser Sec16A.

Newly made secretory and membrane proteins exit the endoplasmic reticulum (ER) in COPII vesicles that form at specialised ER exit sites. These exit sites are typically near the early Golgi compartments that receive these vesicles. A key player in the delivery of vesicles to the early Golgi is p115 (also known as USO1), a homodimer with a folded head domain and a coiled-coil tail that is anchored to Golgi membranes. p115 has been shown to capture vesicles and to bind to SNARE proteins to promote membrane fusion. Here, we report that the head domain of human p115 can bind directly to Sec16A, a large scaffolding protein that organises ER sites and promotes COPII vesicle formation. Structural prediction and deletion mapping defined the region of interaction to a conserved motif in the unstructured N-terminal region of Sec16A, and mutations in p115 that block motif binding reduced the efficiency of secretion. This interaction could potentially allow a subset of p115 molecules to reach across from the early Golgi to ER exit sites to contribute to the large-scale organisation of the early secretory pathway.