Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The COPII cage: unifying principles of vesicle coat assembly

Key Points

  • Endoplasmic reticulum (ER) export by the coat protein complex-II (COPII) machinery involves the transport of nearly a third of the proteins that are encoded by the eukaryotic genome. The wide range of protein-folding stabilities that are accommodated by the COPII machinery indicates that the current view of the ER as a quality-control device should now be tempered with the more general principle that the energetics of the protein fold, independently of the final functional fold, directs ER export under physiological conditions.

  • Cargo selection by the Sec23–Sec24 adaptor protein complex involves a high valency cargo adaptor platform. Through its binding to this cargo adaptor platform, cargo has an important role in directing vesicle formation and membrane traffic.

  • The self-assembly properties of the Sec13–Sec31 complex, which result in the formation of a highly flexible cuboctahedral cage, direct the concentration of cargo into budding vesicles and coordinate cargo recruitment with membrane curvature and fission.

  • The GTPase Sar1, which is involved in Sec23–Sec24 membrane recruitment during the early steps of coat protein complex (CPC) assembly, also has an important role in late events — it directs vesicle fission. Vesicle release that is mediated by Sar1–GTP hydrolysis is likely to be coordinated with the function of lipid-remodelling factors.

  • The structural and biochemical properties that are involved in the function of the COPII export machinery combined with those that have been observed for cargo selection and the generation of coat complexes by clathrin-mediated pathways now provide a unifying model for CPC assembly in eukaryotic cells. The assembly of CPCs is driven by various kinetic parameters that control the individual steps of protein folding, cargo selection and collection, and membrane curvature and fission dynamics. These complexes are therefore highly versatile and robust trafficking machineries.

  • CPCs — which include the COPII, clathrin and COPI coats — probably evolved from the more flexible cage structure that is found in the COPII-based pathway, which directs ER export, to the more selective and rigid clathrin-based and COPI-based cage structures, which are involved in post-ER trafficking pathways.

Abstract

Communication between compartments of the exocytic and endocytic pathways in eukaryotic cells involves transport carriers — vesicles and tubules — that mediate the vectorial movement of cargo. Recent studies of transport-carrier formation in the early secretory pathway have provided new insights into the mechanisms of cargo selection by coat protein complex-II (COPII) adaptor proteins, the construction of cage-protein scaffolds and fission. These studies are beginning to produce a unifying molecular and structural model of coat function in the formation and fission of vesicles and tubules in endomembrane traffic.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The core components that are involved in COPII-coated vesicle assembly.
Figure 2: Characterizing COPII coats.
Figure 3: The structural organization of the COPII and clathrin cages.
Figure 4: Cargo collection and concentration by the COPII cage.
Figure 5: A unifying model for COPII cage assembly.
Figure 6: The shared evolutionary origins of coat protein complexes.

Similar content being viewed by others

References

  1. Kelly, J. W. & Balch, W. E. The integration of cell and chemical biology in protein folding. Nature Chem. Biol. 2, 224–227 (2006).

    CAS  Google Scholar 

  2. Gurkan, C. et al. Large-scale profiling of Rab GTPase trafficking networks: the membrome. Mol. Biol. Cell 16, 3847–3864 (2005). A systems biology approach that was used to understand membrane trafficking and that provides an integrated view of the roles of the Rab-GTPase, SNARE and CPC machineries.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Edeling, M. A., Smith, C. & Owen, D. Life of a clathrin coat: insights from clathrin and AP structures. Nature Rev. Mol. Cell Biol. 7, 32–44 (2006).

    CAS  Google Scholar 

  4. Lee, M. C., Miller, E. A., Goldberg, J., Orci, L. & Schekman, R. Bi-directional protein transport between the ER and Golgi. Annu. Rev. Cell Dev. Biol. 20, 87–123 (2004).

    CAS  PubMed  Google Scholar 

  5. Conner, S. D. & Schmid, S. L. Regulated portals of entry into the cell. Nature 422, 37–44 (2003).

    CAS  PubMed  Google Scholar 

  6. Traub, L. M. Common principles in clathrin-mediated sorting at the Golgi and the plasma membrane. Biochim. Biophys. Acta 1744, 415–437 (2005).

    CAS  PubMed  Google Scholar 

  7. Sekijima, Y. et al. The biological and chemical basis for tissue-selective amyloid disease. Cell 121, 73–85 (2005). This paper quantitatively defines the relationship between protein-folding energetics in the ER and cargo selecton by the COPII machinery. The work questions the role of quality control in ER export.

    CAS  PubMed  Google Scholar 

  8. Smith, C. Structural biology. Two geometric solutions to a transporting problem. Science 311, 182–183 (2006).

    CAS  PubMed  Google Scholar 

  9. Stagg, S. M. et al. Structure of the Sec13/31 COPII coat cage. Nature 439, 234–238 (2006). This study shows, using cryo-EM and single-particle analysis, that the self-assembly of Sec13–Sec31 produces a COPII cage lattice that has a cuboctahedral geometry.

    CAS  PubMed  Google Scholar 

  10. Bielli, A. et al. Regulation of Sar1 NH2 terminus by GTP binding and hydrolysis promotes membrane deformation to control COPII vesicle fission. J. Cell Biol. 171, 919–924 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Lee, M. C. et al. Sar1p N-terminal helix initiates membrane curvature and completes the fission of a COPII vesicle. Cell 122, 605–617 (2005). References 10 and 11 describe the role of the Sar1 N-terminal amphipathic helix in promoting membrane curvature and vesicle fission.

    CAS  PubMed  Google Scholar 

  12. Helenius, A. & Aebi, M. Roles of N-linked glycans in the endoplasmic reticulum. Annu. Rev. Biochem. 73, 1019–1049 (2004).

    CAS  PubMed  Google Scholar 

  13. Dobson, C. M. Protein folding and misfolding. Nature 426, 884–890 (2003).

    CAS  PubMed  Google Scholar 

  14. Watson, P. & Stephens, D. J. ER-to-Golgi transport: form and formation of vesicular and tubular carriers. Biochim. Biophys. Acta 1744, 304–315 (2005).

    CAS  PubMed  Google Scholar 

  15. Liu, W. & Lippincott-Schwartz, J. Illuminating COPII coat dynamics. Nature Struct. Mol. Biol. 12, 106–107 (2005).

    CAS  Google Scholar 

  16. Lippincott-Schwartz, J. Dynamics of secretory membrane trafficking. Ann. N. Y. Acad. Sci. 1038, 115–124 (2004).

    PubMed  Google Scholar 

  17. Connerly, P. L. et al. Sec16 is a determinant of transitional ER organization. Curr. Biol. 15, 1439–1447 (2005).

    CAS  PubMed  Google Scholar 

  18. Aridor, M., Bannykh, S. I., Rowe, T. & Balch, W. E. Cargo can modulate COPII vesicle formation from the endoplasmic reticulum. J. Biol. Chem. 274, 4389–4399 (1999).

    CAS  PubMed  Google Scholar 

  19. Sato, K. & Nakano, A. Dissection of COPII subunit-cargo assembly and disassembly kinetics during Sar1p-GTP hydrolysis. Nature Struct. Mol. Biol. 12, 167–174 (2005).

    CAS  Google Scholar 

  20. Forster, R. et al. Secretory cargo regulates the turnover of COPII subunits at single ER exit sites. Curr. Biol. 16, 173–179 (2006). Describes the role of cargo in regulating COPII stability at the resolution of single ERESs. This work led to a preliminary kinetic model for cargo selection.

    CAS  PubMed  Google Scholar 

  21. Ward, T. H., Polishchuk, R. S., Caplan, S., Hirschberg, K. & Lippincott-Schwartz, J. Maintenance of Golgi structure and function depends on the integrity of ER export. J. Cell Biol. 155, 557–570 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Matsuoka, K. et al. COPII-coated vesicle formation reconstituted with purified coat proteins and chemically defined liposomes. Cell 93, 263–275 (1998).

    CAS  PubMed  Google Scholar 

  23. Palmer, K. J. & Stephens, D. J. Biogenesis of ER-to-Golgi transport carriers: complex roles of COPII in ER export. Trends Cell Biol. 14, 57–61 (2004).

    CAS  PubMed  Google Scholar 

  24. Herrmann, J. M., Malkus, P. & Schekman, R. Out of the ER — outfitters, escorts and guides. Trends Cell Biol. 9, 5–7 (1999).

    CAS  PubMed  Google Scholar 

  25. Weissman, J. T., Plutner, H. & Balch, W. E. The mammalian guanine nucleotide exchange factor mSec12 is essential for activation of the Sar1 GTPase directing endoplasmic reticulum export. Traffic 2, 465–475 (2001).

    CAS  PubMed  Google Scholar 

  26. Barlowe, C. & Schekman, R. SEC12 encodes a guanine-nucleotide-exchange factor essential for transport vesicle budding from the ER. Nature 365, 347–349 (1993).

    CAS  PubMed  Google Scholar 

  27. Aridor, M. et al. The Sar1 GTPase coordinates biosynthetic cargo selection with endoplasmic reticulum export site assembly. J. Cell Biol. 152, 213–229 (2001). An initial description of the role of Sar1 in inducing membrane curvature in vivo to generate transitional ER elements that collect cargo for export.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Huang, M. et al. Crystal structure of Sar1-GDP at 1.7 Å resolution and the role of the NH2 terminus in ER export. J. Cell Biol. 155, 937–948 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Bi, X., Corpina, R. A. & Goldberg, J. Structure of the Sec23/24–Sar1 pre-budding complex of the COPII vesicle coat. Nature 419, 271–277 (2002). An important description of the structure of the Sar1–Sec23–Sec24 complex, which was determined using X-ray crystallography.

    CAS  PubMed  Google Scholar 

  30. Peng, R., De Antoni, A. & Gallwitz, D. Evidence for overlapping and distinct functions in protein transport of coat protein Sec24p family members. J. Biol. Chem. 275, 11521–11528 (2000).

    CAS  PubMed  Google Scholar 

  31. Roberg, K. J., Crotwell, M., Espenshade, P., Gimeno, R. & Kaiser, C. A. LST1 is a SEC24 homologue used for selective export of the plasma membrane ATPase from the endoplasmic reticulum. J. Cell Biol. 145, 659–672 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Shimoni, Y. et al. Lst1p and Sec24p cooperate in sorting of the plasma membrane ATPase into COPII vesicles in Saccharomyces cerevisiae. J. Cell Biol. 151, 973–984 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Bickford, L. C., Mossessova, E. & Goldberg, J. A structural view of the COPII vesicle coat. Curr. Opin. Struct. Biol. 14, 147–153 (2004).

    CAS  PubMed  Google Scholar 

  34. Zimmerberg, J. & Kozlov, M. M. How proteins produce cellular membrane curvature. Nature Rev. Mol. Cell Biol. 7, 9–19 (2006).

    CAS  Google Scholar 

  35. Scheffzek, K., Ahmadian, M. R. & Wittinghofer, A. GTPase-activating proteins: helping hands to complement an active site. Trends Biochem. Sci. 23, 257–262 (1998).

    CAS  PubMed  Google Scholar 

  36. Kappeler, F., Klopfenstein, D. R., Foguet, M., Paccaud, J. P. & Hauri, H. P. The recycling of ERGIC-53 in the early secretory pathway. ERGIC-53 carries a cytosolic endoplasmic reticulum-exit determinant interacting with COPII. J. Biol. Chem. 272, 31801–31808 (1997).

    CAS  PubMed  Google Scholar 

  37. Sato, K. & Nakano, A. Emp47p and its close homolog Emp46p have a tyrosine-containing endoplasmic reticulum exit signal and function in glycoprotein secretion in Saccharomyces cerevisiae. Mol. Biol. Cell 13, 2518–2532 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Nishimura, N. et al. A di-acidic (DXE) code directs concentration of cargo during export from the endoplasmic reticulum. J. Biol. Chem. 274, 15937–15946 (1999).

    CAS  PubMed  Google Scholar 

  39. Nishimura, N. & Balch, W. E. A di-acidic signal required for selective export from the endoplasmic reticulum. Science 277, 556–558 (1997).

    CAS  PubMed  Google Scholar 

  40. Votsmeier, C. & Gallwitz, D. An acidic sequence of a putative yeast Golgi membrane protein binds COPII and facilitates ER export. EMBO J. 20, 6742–6750 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Yeung, T., Barlowe, C. & Schekman, R. Uncoupled packaging of targeting and cargo molecules during transport vesicle budding from the endoplasmic reticulum. J. Biol. Chem. 270, 30567–30570 (1995).

    CAS  PubMed  Google Scholar 

  42. Mossessova, E., Bickford, L. C. & Goldberg, J. SNARE selectivity of the COPII coat. Cell 114, 483–495 (2003).

    CAS  PubMed  Google Scholar 

  43. Martinez-Menarguez, J. A., Geuze, H. J., Slot, J. W. & Klumperman, J. Vesicular tubular clusters between the ER and Golgi mediate concentration of soluble secretory proteins by exclusion from COPI-coated vesicles. Cell 98, 81–90 (1999).

    CAS  PubMed  Google Scholar 

  44. Oprins, A. et al. The ER to Golgi interface is the major concentration site of secretory proteins in the exocrine pancreatic cell. Traffic 2, 831–838 (2001).

    CAS  PubMed  Google Scholar 

  45. Bonifacino, J. S. & Glick, B. S. The mechanisms of vesicle budding and fusion. Cell 116, 153–166 (2004).

    CAS  PubMed  Google Scholar 

  46. Matsuoka, K., Schekman, R., Orci, L. & Heuser, J. E. Surface structure of the COPII-coated vesicle. Proc. Natl Acad. Sci. USA 98, 13705–13709 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Antonny, B., Gounon, P., Schekman, R. & Orci, L. Self-assembly of minimal COPII cages. EMBO Rep. 4, 419–424 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Tang, B. L. et al. The mammalian homolog of yeast Sec13p is enriched in the intermediate compartment and is essential for protein transport from the endoplasmic reticulum to the Golgi apparatus. Mol. Cell. Biol. 17, 256–266 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Shaywitz, D. A., Orci, L., Ravazzola, M., Swaroop, A. & Kaiser, C. A. Human SEC13Rp functions in yeast and is located on transport vesicles budding from the endoplasmic reticulum. J. Cell Biol. 128, 769–777 (1995).

    CAS  PubMed  Google Scholar 

  50. Swaroop, A. et al. Molecular characterization of a novel human gene, SEC13R, related to the yeast secretory pathway gene SEC13, and mapping to a conserved linkage group on human chromosome 3p24–p25 and mouse chromosome 6. Hum. Mol. Genet. 3, 1281–1286 (1994).

    CAS  PubMed  Google Scholar 

  51. Siniossoglou, S. et al. A novel complex of nucleoporins, which includes Sec13p and a Sec13p homolog, is essential for normal nuclear pores. Cell 84, 265–275 (1996).

    CAS  PubMed  Google Scholar 

  52. Devos, D. et al. Simple fold composition and modular architecture of the nuclear pore complex. Proc. Natl Acad. Sci. USA 103, 2172–2177 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Loiodice, I. et al. The entire Nup107–160 complex, including three new members, is targeted as one entity to kinetochores in mitosis. Mol. Biol. Cell 15, 3333–3344 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Devos, D. et al. Components of coated vesicles and nuclear pore complexes share a common molecular architecture. PLoS Biol. 2, e380 (2004). Using computational structure prediction and biochemical analysis, this paper provides insights into the common structural motifs that have been used to create CPCs.

    PubMed  PubMed Central  Google Scholar 

  55. Siniossoglou, S. et al. Structure and assembly of the Nup84p complex. J. Cell Biol. 149, 41–54 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Mammoto, A., Ohtsuka, T., Hotta, I., Sasaki, T. & Takai, Y. Rab11BP/Rabphilin-11, a downstream target of Rab11 small G protein implicated in vesicle recycling. J. Biol. Chem. 274, 25517–25524 (1999).

    CAS  PubMed  Google Scholar 

  57. Prekeris, R. Rabs, Rips, FIPs, and endocytic membrane traffic. Scientific World J. 3, 870–880 (2003).

    Google Scholar 

  58. Stankewich, M. C., Stabach, P. R. & Morrow, J. S. Human Sec31B: a family of new mammalian orthologues of yeast Sec31p that associate with the COPII coat. J. Cell Sci. 119, 958–969 (2006).

    CAS  PubMed  Google Scholar 

  59. Shugrue, C. A. et al. Identification of the putative mammalian orthologue of Sec31P, a component of the COPII coat. J. Cell Sci. 112, 4547–4556 (1999).

    CAS  PubMed  Google Scholar 

  60. Tang, B. L. et al. Mammalian homologues of yeast Sec31p. An ubiquitously expressed form is localized to endoplasmic reticulum (ER) exit sites and is essential for ER–Golgi transport. J. Biol. Chem. 275, 13597–13604 (2000).

    CAS  PubMed  Google Scholar 

  61. Lederkremer, G. Z. et al. Structure of the Sec23p/24p and Sec13p/31p complexes of COPII. Proc. Natl Acad. Sci. USA 98, 10704–10709 (2001). Provides low-resolution views of the structures of the Sec23–Sec24 and Sec13–Sec31 complexes using EM.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Fotin, A. et al. Molecular model for a complete clathrin lattice from electron cryomicroscopy. Nature 432, 573–579 (2004).

    CAS  PubMed  Google Scholar 

  63. Kirchhausen, T. Clathrin. Annu. Rev. Biochem. 69, 699–727 (2000).

    CAS  PubMed  Google Scholar 

  64. Shoulders, C. C., Stephens, D. J. & Jones, B. The intracellular transport of chylomicrons requires the small GTPase, Sar1b. Curr. Opin. Lipidol. 15, 191–197 (2004).

    CAS  PubMed  Google Scholar 

  65. Aridor, M., Guzik, A. K., Bielli, A. & Fish, K. N. Endoplasmic reticulum export site formation and function in dendrites. J. Neurosci. 24, 3770–3776 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Antonny, B. Membrane deformation by protein coats. Curr. Opin. Cell Biol. 18, 386–394 (2006). An important and thoughtful review on the role of protein coats in the generation of membrane curvature.

    CAS  PubMed  Google Scholar 

  67. Schroder, M. & Kaufman, R. J. The mammalian unfolded protein response. Annu. Rev. Biochem. 74, 739–789 (2005).

    PubMed  Google Scholar 

  68. Schledzewski, K., Brinkmann, H. & Mendel, R. R. Phylogenetic analysis of components of the eukaryotic vesicle transport system reveals a common origin of adaptor protein complexes 1, 2, and 3 and the F subcomplex of the coatomer COPI. J. Mol. Evol. 48, 770–778 (1999).

    CAS  PubMed  Google Scholar 

  69. Eugster, A., Frigerio, G., Dale, M. & Duden, R. COP I domains required for coatomer integrity, and novel interactions with ARF and ARF-GAP. EMBO J. 19, 3905–3917 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Mans, B. J., Anantharaman, V., Aravind, L. & Koonin, E. V. Comparative genomics, evolution and origins of the nuclear envelope and nuclear pore complex. Cell Cycle 3, 1612–1637 (2004).

    CAS  PubMed  Google Scholar 

  71. Clarke, P. R. & Zhang, C. Spatial and temporal control of nuclear envelope assembly by Ran GTPase. Symp. Soc. Exp. Biol. 56, 193–204 (2004).

    CAS  Google Scholar 

  72. Schwartz, N. Estimating curvature of nondifferentiable functions and complex shape contours. Percept. Mot. Skills 101, 362–364 (2005).

    PubMed  Google Scholar 

  73. Jekely, G. Small GTPases and the evolution of the eukaryotic cell. Bioessays 25, 1129–1138 (2003).

    CAS  PubMed  Google Scholar 

  74. Cavalier-Smith, T. The phagotrophic origin of eukaryotes and phylogenetic classification of Protozoa. Int. J. Syst. Evol. Microbiol. 52, 297–354 (2002).

    CAS  PubMed  Google Scholar 

  75. Cavalier-Smith, T. & Chao, E. E. Phylogeny and megasystematics of phagotrophic heterokonts (kingdom Chromista). J. Mol. Evol. 62, 388–420 (2006).

    CAS  PubMed  Google Scholar 

  76. Hartzell, P. L. Complementation of sporulation and motility defects in a prokaryote by a eukaryotic GTPase. Proc. Natl Acad. Sci. USA 94, 9881–9886 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Palade, G. Intracellular aspects of the process of protein synthesis. Science 189, 347–358 (1975).

    CAS  PubMed  Google Scholar 

  78. Brunger, A. T. Structure and function of SNARE and SNARE-interacting proteins. Q. Rev. Biophys. 38, 1–47 (2005).

    CAS  PubMed  Google Scholar 

  79. Sztul, E. & Lupashin, V. Role of tethering factors in secretory membrane traffic. Am. J. Physiol. Cell Physiol. 290, C11–C26 (2006).

    CAS  PubMed  Google Scholar 

  80. Bonifacino, J. S. & Lippincott-Schwartz, J. Coat proteins: shaping membrane transport. Nature Rev. Mol. Cell Biol. 4, 409–414 (2003).

    CAS  Google Scholar 

  81. Bannykh, S. I., Rowe, T. & Balch, W. E. The organization of endoplasmic reticulum export complexes. J. Cell Biol. 135, 19–35 (1996).

    CAS  PubMed  Google Scholar 

  82. Zeuschner, D. et al. Immuno-electron tomography of ER exit sites reveals the existence of free COPII-coated transport carriers. Nature Cell Biol. 8, 377–383 (2006). An important paper that resolves the controversy about the presence of COPII-coated vesicles at ERESs.

    CAS  PubMed  Google Scholar 

  83. Allan, B. B., Moyer, B. D. & Balch, W. E. Rab1 recruitment of p115 into a cis-SNARE complex: programming budding COPII vesicles for fusion. Science 289, 444–448 (2000).

    CAS  PubMed  Google Scholar 

  84. Bannykh, S. I. & Balch, W. E. Selective transport of cargo between the endoplasmic reticulum and Golgi compartments. Histochem. Cell Biol. 109, 463–475 (1998).

    CAS  PubMed  Google Scholar 

  85. Storrie, B. Maintenance of Golgi apparatus structure in the face of continuous protein recycling to the endoplasmic reticulum: making ends meet. Int. Rev. Cytol. 244, 69–94 (2005).

    CAS  PubMed  Google Scholar 

  86. Mironov, A. A. et al. ER-to-Golgi carriers arise through direct en bloc protrusion and multistage maturation of specialized ER exit domains. Dev. Cell 5, 583–594 (2003). Describes the morphological existence of large non-COPII-coated ERESs that are involved in the COPII-dependent export of large cargo.

    CAS  PubMed  Google Scholar 

  87. Chardin, P. & Callebaut, I. The yeast Sar exchange factor Sec12, and its higher organism orthologs, fold as β-propellers. FEBS Lett. 525, 171–173 (2002).

    CAS  PubMed  Google Scholar 

  88. Mancias, J. D. & Goldberg, J. Exiting the endoplasmic reticulum. Traffic 6, 278–285 (2005).

    CAS  PubMed  Google Scholar 

  89. Gurkan, C., Koulov, A. V. & Balch, W. E. in Origins and Evolution of Eukaryotic Endomembranes and Cytoskeleton (ed. Jékely, G.) (Landes Bioscience, Georgetown, 2006).

    Google Scholar 

  90. Wang, X. et al. COPII-dependent export of cystic fibrosis transmembrane conductance regulator from the ER uses a di-acidic exit code. J. Cell Biol. 167, 65–74 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. McMahon, H. T. & Mills, I. G. COP and clathrin-coated vesicle budding: different pathways, common approaches. Curr. Opin. Cell Biol. 16, 379–391 (2004).

    CAS  PubMed  Google Scholar 

  92. Guo, Y. & Linstedt, A. D. COPII–Golgi protein interactions regulate COPII coat assembly and Golgi size. J. Cell Biol. 174, 53–63 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by a National Institutes of Health (NIH) grant to W.E.B. and an NIH postdoctoral fellowship to S.M.S. Postdoctoral fellowships to P.L. and C.G. were from the Cystic Fibrosis Foundation. We thank G. Palade for providing an image of the ER–Golgi system in the pancreas (Box 1).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to William E. Balch.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Related links

Related links

DATABASES

Protein Data Bank

1F6B

1M2O

FURTHER INFORMATION

The Balch Lab

Genomics Institute of the Novartis Research Foundation — Body-Wide Profiling of the Human and Mouse Membromes

Macromolecular Structure Database — Structure of the Sec13/31 COPII coat cage

Macromolecular Structure Database — EM-Search Tool for Electron Microscopy Depositions

Movie of the Sec13–Sec31 COPII cage

The Scripps Research Institute Automated Molecular Imaging group

Glossary

Coat protein complexes (CPCs)

CPCs are a collection of cytosolic proteins that interact to form a coat on membranes and drive cargo selection and vesicle formation.

Clathrin

The main cage component of the coat that is associated with clathrin-coated vesicles, which are involved in membrane transport in both the endocytic and the exocytic pathways. Clathrin forms vesicles that originate on the trans-Golgi network and the plasma membrane.

Coat protein complex-I (COPI)

A specialized coat protein complex that is involved in the retrograde transport of cargo between the compartments of the Golgi and from the Golgi to the endoplasmic reticulum.

Coat protein complex-II (COPII)

A specialized coat protein complex that is involved in the anterograde transport of cargo from the endoplasmic reticulum to the Golgi.

Adaptor protein (AP) complexes

An AP complex is a collection of interacting proteins that link cargo to the polymeric lattice that forms a vesicle cage.

Ras superfamily

A superfamily of small, monomeric GTPases that are involved in membrane trafficking, growth, differentiation and cellular signalling.

Cuboctahedral geometry

An Archimedean solid, with 24 identical edges or 12 identical vertices, in which 8 triangular faces and 6 square faces are arranged such that 2 triangles and 2 squares meet at each vertex and each edge separates a triangle and a square.

Guanine nucleotide-exchange factor

(GEF). A GEF interacts with a GTPase to promote the exchange of bound GDP for GTP.

Endoplasmic-reticulum-associated folding pathway (ERAF)

A pathway in which endoplasmic reticulum (ER)-associated chaperones direct the folding of soluble and transmembrane cargo proteins that have been translocated into the ER.

GTPase-activating protein

(GAP). A GAP interacts with an activated GTPase to promote the hydrolysis of the bound GTP, which converts the GTPase protein to its GDP-bound state.

SNAREs

(Soluble N-ethylmaleimide-sensitive factor attachment protein receptors). A protein family that consists of a cognate group of integral and peripheral membrane proteins that are required for bilayer recognition and fusion during membrane traffic.

Nuclear pore complex

(NPC). The NPC is a multiprotein complex that stabilizes the continuity between the inner and outer nuclear membranes by forming protein-permeable pores in the nuclear envelope.

Rab GTPases

Rab proteins form the largest subfamily of small GTPases of the Ras superfamily. They regulate membrane budding, tethering, fusion, and vesicle and tubule motility at various sites within cells.

WD40 domain

A protein structural arrangement in which several 'blades', which each consist of a four-stranded antiparallel β-sheet that is formed by WD40 repeats, are arranged radially around a central axis. WD40 repeats are short 40-amino-acid motifs that often terminate in a Trp–Asp (W–D) dipeptide.

α-solenoid structure

A protein structural motif in which numerous pairs of antiparallel α-helices are stacked to form a solenoid.

Chylomicrons

Lipoproteins that are involved in the transfer of lipids that are absorbed in the small intestine.

ARF GTPases

ADP-ribosylation factor (ARF) GTPases constitute a subfamily of the Ras-GTPase superfamily. They are involved in the regulation of intracellular transport by modulating the interactions of adaptor protein complexes with cage assemblies.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gürkan, C., Stagg, S., LaPointe, P. et al. The COPII cage: unifying principles of vesicle coat assembly. Nat Rev Mol Cell Biol 7, 727–738 (2006). https://doi.org/10.1038/nrm2025

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrm2025

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing