COPII-dependent ER export in animal cells: adaptation and control for diverse cargo

Abstract

The export of newly synthesized proteins from the endoplasmic reticulum is fundamental to the ongoing maintenance of cell and tissue structure and function. After co-translational translocation into the ER, proteins destined for downstream intracellular compartments or secretion from the cell are sorted and packaged into transport vesicles by the COPII coat protein complex. The fundamental discovery and characterization of the pathway has now been augmented by a greater understanding of the role of COPII in diverse aspects of cell function. We now have a deep understanding of how COPII contributes to the trafficking of diverse cargoes including extracellular matrix molecules, developmental signalling proteins, and key metabolic factors such as lipoproteins. Structural and functional studies have shown that the COPII coat is both highly flexible and subject to multiple modes of regulation. This has led to new discoveries defining roles of COPII in development, autophagy, and tissue organization. Many of these newly emerging features of the canonical COPII pathway are placed in a context of procollagen secretion because of the fundamental interest in how a coat complex that typically generates 80-nm transport vesicles can package a cargo reported to be over 300 nm. Here we review the current understanding of COPII and assess the current consensus on its role in packaging diverse cargo proteins.

Hepatitis B subviral envelope particles use the COPII machinery for intracellular transport via selective exploitation of Sec24A and Sec23B

“…The second, more efficient mechanism is an active sorting of cargo proteins based on specific signals. Upon ER export, specific Sec proteins function in a highly conserved signal pathway in order to form COPII‐coated vesicles, budding out of the ER membrane at ER exit sites (ERESs; Barlowe & Helenius, ; Bethune & Wieland, ; McCaughey & Stephens, ; Miller & Schekman, ). COPII assembly starts with the activation of the small GTPase Sar1 and its recruitment to the ER with assistance of its membrane‐bound guanine nucleotide exchange factor Sec12.…”

“…Sec24 hereby specifically binds to cargo proteins via distinct binding motifs, whereas Sec23 modulates the GTP cycle of Sar1. After this, the tetrameric Sec13/Sec31 complex gets recruited to the Sar1–Sec23/24 complex in order to form the outer coat layer, sustain the membrane curvature, inactivate Sar1, and finally promote the vesicle budding (Figure ; Barlowe & Helenius, ; Bethune & Wieland, ; McCaughey & Stephens, ; Miller & Schekman, ).…”

DYRK3-Controlled Phase Separation Organizes the Early Secretory Pathway

“…At the ER, cargo is packed into coat protein complex II (COPII)-coated transport vesicles at specialized domains called ER exit sites (ERES). Extensive genetic, cell biological and biochemical work has characterized the machinery required for ERES and COPII vesicle formation and for establishing plasticity to adapt the size of transport carriers to the type of cargo (3)(4)(5)(6)(7)(8)(9)(10). In this process, the peripheral membrane protein Sec16A plays an essential role by forming oligomers that may act as scaffolds for recruiting the components necessary for COPII vesicle formation (5,(11)(12)(13)(14)(15)(16).…”

Genome-wide identification of alternative splicing events that regulate protein transport across the secretory pathway

“…After biosynthesis in the endoplasmic reticulum (ER), proteins are transported to their destination via the secretory pathway. Transport processes are highly flexible and adapt to new requirements, for instance during differentiation or after activation (Farhan and Rabouille, 2011;McCaughey and Stephens, 2018). This adaptation has been studied in regard to differential gene expression (Dunne et al, 2002;Coutinho et al, 2004;Schotman et al, 2009), changes in membrane morphology and dynamics (Forster et al, 2006;Guo and Linstedt, 2006;Farhan et al, 2008), and altered activity of kinases and phosphatases (Farhan et al, 2010).…”