COPII vesicles bud from specialized regions in the ER membrane that lack bound ribosomes. These regions are called ER exit sites and are dispersed throughout the ER membrane.

After budding, some transport vesicles shed their coat and fuse with one another to form larger vesicles. Fusion between identical membrane types is called homotypic fusion.

In contrast, heterotypic fusion occurs when non-identical membranes fuse, such as a Golgi-derived vesicle fusing into the ER membrane.

In homotypic fusion, N-ethylmaleimide sensitive factor or NSF proteins force t-SNAREs and v-SNAREs apart from each other. Complementary SNAREs on the adjacent vesicle interact, and the identical membranes fuse.

Such fusion between COPII vesicles forms an extended membranous structure called a vesicular tubular cluster or VTC.

This occurs in a region between the ER and Golgi, called the ER-Golgi intermediate compartment or ERGIC.

The VTC moves along microtubule tracks, carrying ER proteins that are not fully folded and functional, cargo receptors, and SNAREs.

As it moves, new COPI vesicles spontaneously bud off from the tubular clusters. The mechanism of switching the coat protein is yet unknown.

These new transport vesicles carry escaped cargo involved in the ER budding and vesicle fusion back to the ER in a process called the ER retrieval pathway.