ER-to-Golgi Transport: A Sizeable Problem

Export of cargo from the ER requires an adaptable system to accommodate cargoes of diverse size and shape. In metazoans, the secretion of collagens has been widely studied due to their large size. TANGO1 has emerged as a key player in assembling COPII-dependent machinery to drive export from the ER. The interplay between TANGO1 and the chaperone Hsp47 is central to understanding this process. New data and resulting models have challenged the ‘large carrier’ model and have led to questions of whether complete coating of carriers with COPII is needed. Metazoans require efficient and ordered secretion of extracellular matrix (ECM) to coordinate cell and tissue function. Many ECM proteins are atypically large and their demand during key stages of development presents a major challenge to the canonical secretion machinery. While many of the molecular players in this pathway are known, little is understood about how they are integrated in time and space. Recent advances in gene engineering and super-resolution microscopy have underscored the spatiotemporal organisation of the endoplasmic reticulum (ER)–Golgi interface. These findings are challenging long-held models of vesicular transport of large matrix proteins, such as procollagen, and are implicating less well-defined carriers and direct interconnections between organelles. Here, we discuss current models describing the dynamics and mechanisms of ER–Golgi transport. Metazoans require efficient and ordered secretion of extracellular matrix (ECM) to coordinate cell and tissue function. Many ECM proteins are atypically large and their demand during key stages of development presents a major challenge to the canonical secretion machinery. While many of the molecular players in this pathway are known, little is understood about how they are integrated in time and space. Recent advances in gene engineering and super-resolution microscopy have underscored the spatiotemporal organisation of the endoplasmic reticulum (ER)–Golgi interface. These findings are challenging long-held models of vesicular transport of large matrix proteins, such as procollagen, and are implicating less well-defined carriers and direct interconnections between organelles. Here, we discuss current models describing the dynamics and mechanisms of ER–Golgi transport. a multiprotein complex that assembles in a GTP-dependent manner on the cytosolic face of the ER to concentrate cargo and initiate transport carrier formation. comprising the transitional ER, budding structures, and the first post-ER membranes of the ERGIC. the first post-ER compartment; plays a key role in the models of large-vesicle formation. It could act to maintain the physical separation of ER and Golgi to prevent compartment mixing. a chaperone that specifically enables the folding and assembly of procollagen and acts in its ER export through interactions with both collagen and TANGO1. It can also bind to other ECM proteins. a ubiquitylation adaptor that was described to promote large-carrier formation (Box 1). we use this term to define those unusually large proteins that are packaged by the COPII system but would be too large to fit within an 80-nm transport vesicle. also known as brittle bone disease; a disease of procollagen biology that results in bones that break very easily; >90% of cases are caused by mutations in the genes that encode type I procollagen. the precursor of collagen, synthesised in the ER. There are 28 different types of collagen; this review focusses on the large collagens including fibrillar type I and II. a component of the TRAPP tethering complex that mediates the fusion of post-ER membranes. It binds to TANGO1 and mutations in humans cause X-linked spondyloepiphyseal dysplasia. a cargo adaptor for procollagen, and likely other cargo, that spans the ER membrane, physically linking cargo to the COPII coat.