Abstract
One third of all proteins in eukaryotes transit between the endoplasmic reticulum (ER) and the Golgi to reach their functional destination inside or outside of the cell. During export, secretory proteins concentrate at transitional zones of the ER known as ER exit sites, where they are packaged into transport carriers formed by the highly conserved coat protein complex II (COPII). Despite long-standing knowledge of many of the fundamental pathways that govern traffic in the early secretory pathway, we still lack a complete mechanistic model to explain how the various steps of COPII-mediated ER exit are regulated to efficiently transport diverse cargoes. In this Review, we discuss the current understanding of the mechanisms underlying COPII-mediated vesicular transport, highlighting outstanding knowledge gaps. We focus on how coat assembly and disassembly dictate carrier morphogenesis, how COPII selectively recruits a vast number of cargo and cargo adaptors, and finally discuss how COPII mechanisms in mammals might have adapted to enable transport of large proteins.