Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
ReviewVesicle-mediated ER export of proteins and lipids☆
Highlights
► Transport of lipids and proteins from the ER is a highly regulated process. ► Protein exit from the ER occurs via signal-mediate export and bulk flow. ► The COPII machinery can adapt to export large or bulky cargoes. ► ER export of lipids occurs via both vesicular and non-vesicular mechanisms.
Section snippets
Introduction: the COPII coat marks the way out
The ER is a remarkably productive organelle, being the site of secretory protein synthesis and a major source of intracellular lipid synthesis. Furthermore, it maintains a highly dynamic structure, comprising the nuclear envelope, membrane sheets, tubules and cisternae that are fully interconnected [1], [2], [3]. To maintain this structure and functionality requires tight regulation of a number of processes including protein and lipid transport. Within the spectrum of diverse eukaryotic cells,
ER export of protein cargo
The process of accurate and selective recruitment of cargo proteins into nascent COPII vesicles is an integral part of the fidelity of ER export and transport through the secretory pathway. Indeed, the sheer volume and diversity of molecules that traffic through the ER is a testament to the flexibility of this process: it is estimated up to one-third of all proteins in yeast, ~ 70% of hepatocyte proteins and ~ 6000 proteins in human cells traffic through the ER for secretion or delivery to other
Lipid traffic from the ER
Although primarily studied for its role in the synthesis of secretory proteins, the ER is also central to endomembrane homeostasis as a key site of lipid synthesis. Over 1000 different lipid species comprise cellular membranes [105], forming three major groups based on their chemical structures—glycerophospholipids, sterols and sphingolipids. The distribution of these lipids varies within the cell, with different intracellular compartments enclosed by membranes with distinct compositions with
Conclusions and perspectives
New challenges are now emerging in understanding export from the ER. The minimal components of canonical COPII vesicle formation have been characterized extensively, and recent efforts are focusing on not only the flexibility of the COPII machinery but also how this machinery is coordinated in vivo. While recapitulating the minimal COPII machinery in vitro can describe the molecular detail of vesicle formation, it cannot report on any diversity in the vesicles formed in the cell. For example,
Acknowledgement
Work in the Miller lab is supported by NIH grants GM085089 and GM078186.
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Cited by (0)
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This article is part of a Special Issue entitled Lipids and Vesicular Transport.
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These authors contributed equally.