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:

COPII and the regulation of protein sorting in mammals

An Erratum to this article was published on 02 February 2012

This article has been updated

Abstract

Secretory proteins are transported to the Golgi complex in vesicles that bud from the endoplasmic reticulum. The cytoplasmic coat protein complex II (COPII) is responsible for cargo sorting and vesicle morphogenesis. COPII was first described in Saccharomyces cerevisiae, but its basic function is conserved throughout all eukaryotes. Nevertheless, the COPII coat has adapted to the higher complexity of mammalian physiology, achieving more sophisticated levels of secretory regulation. In this review we cover aspects of mammalian COPII-mediated regulation of secretion, in particular related to the function of COPII paralogues, the spatial organization of cargo export and the role of accessory proteins.

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: Structure of COPII components.
Figure 2: ERES morphology.
Figure 3: Adaptor proteins mediate cargo sorting in COPII vesicles at ER exit sites.
Figure 4: Basis for cage flexibility and incorporation of large cargoes.

Similar content being viewed by others

Change history

  • 06 January 2012

    In the version of this review initially published online and in print, the key in figure 2 was incorrect. These errors have been corrected in the HTML and PDF versions of the article.

References

  1. Barlowe, C. et al. COPII: a membrane coat formed by Sec proteins that drive vesicle budding from the endoplasmic reticulum. Cell 77, 895–907 (1994).

    Article  CAS  PubMed  Google Scholar 

  2. Orci, L. et al. Mammalian Sec23p homologue is restricted to the endoplasmic reticulum transitional cytoplasm. Proc. Natl Acad. Sci. USA 88, 8611–8615 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. 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 

  4. Goldberg, J. Structural basis for activation of ARF GTPase: mechanisms of guanine nucleotide exchange and GTP-myristoyl switching. Cell 95, 237–248 (1998).

    CAS  PubMed  Google Scholar 

  5. 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 

  6. 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).

    CAS  PubMed  Google Scholar 

  7. Rao, Y. et al. An open conformation of switch I revealed by Sar1-GDP crystal structure at low Mg2+. Biochem. Biophys. Res. Commun. 348, 908–915 (2006).

    CAS  PubMed  Google Scholar 

  8. Antonny, B., Beraud-Dufour, S., Chardin, P. & Chabre, M. N-terminal hydrophobic residues of the G-protein ADP-ribosylation factor-1 insert into membrane phospholipids upon GDP to GTP exchange. Biochemistry 36, 4675–4684 (1997).

    CAS  PubMed  Google Scholar 

  9. 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 

  10. 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).

    CAS  PubMed  Google Scholar 

  11. Miller, E., Antonny, B., Hamamoto, S. & Schekman, R. Cargo selection into COPII vesicles is driven by the Sec24p subunit. EMBO J. 21, 6105–6113 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 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 

  13. Fath, S., Mancias, J. D., Bi, X. & Goldberg, J. Structure and organization of coat proteins in the COPII cage. Cell 129, 1325–1336 (2007).

    CAS  PubMed  Google Scholar 

  14. Stagg, S. M. et al. Structure of the Sec13/31 COPII coat cage. Nature 439, 234–238 (2006).

    CAS  PubMed  Google Scholar 

  15. Stagg, S. M. et al. Structural basis for cargo regulation of COPII coat assembly. Cell 134, 474–484 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Antonny, B., Madden, D., Hamamoto, S., Orci, L. & Schekman, R. Dynamics of the COPII coat with GTP and stable analogues. Nat. Cell Biol. 3, 531–537 (2001).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  18. Forster, R. et al. Secretory cargo regulates the turnover of COPII subunits at single ER exit sites. Curr. Biol. 16, 173–179 (2006).

    CAS  PubMed  Google Scholar 

  19. Cai, H. et al. TRAPPI tethers COPII vesicles by binding the coat subunit Sec23. Nature 445, 941–944 (2007).

    CAS  PubMed  Google Scholar 

  20. Lord, C. et al. Sequential interactions with Sec23 control the direction of vesicle traffic. Nature 473, 181–186 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Bi, X., Mancias, J. D. & Goldberg, J. Insights into COPII coat nucleation from the structure of Sec23.Sar1 complexed with the active fragment of Sec31. Dev. Cell 13, 635–645 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Fromme, J. C. et al. The genetic basis of a craniofacial disease provides insight into COPII coat assembly. Dev. Cell 13, 623–634 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Fromme, J. C., Orci, L. & Schekman, R. Coordination of COPII vesicle trafficking by Sec23. Trends Cell Biol. 18, 330–336 (2008).

    CAS  PubMed  Google Scholar 

  24. Lang, M. R., Lapierre, L. A., Frotscher, M., Goldenring, J. R. & Knapik, E. W. Secretory COPII coat component Sec23a is essential for craniofacial chondrocyte maturation. Nat. Genet. 38, 1198–1203 (2006).

    CAS  PubMed  Google Scholar 

  25. Bianchi, P. et al. Congenital dyserythropoietic anemia type II (CDAII) is caused by mutations in the SEC23B gene. Hum. Mutat. 30, 1292–1298 (2009).

    CAS  PubMed  Google Scholar 

  26. Schwarz, K. et al. Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type II. Nat. Genet. 41, 936–940 (2009).

    CAS  PubMed  Google Scholar 

  27. Miller, E. A. et al. Multiple cargo binding sites on the COPII subunit Sec24p ensure capture of diverse membrane proteins into transport vesicles. Cell 114, 497–509 (2003).

    CAS  PubMed  Google Scholar 

  28. Wendeler, M. W., Paccaud, J. P. & Hauri, H. P. Role of Sec24 isoforms in selective export of membrane proteins from the endoplasmic reticulum. EMBO Rep. 8, 258–264 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Demmel, L. et al. Differential selection of Golgi proteins by COPII Sec24 isoforms in procyclic T. brucei. Traffic 12, 1575–1591 (2011).

    CAS  Google Scholar 

  30. Mancias, J. D. & Goldberg, J. The transport signal on Sec22 for packaging into COPII-coated vesicles is a conformational epitope. Mol. Cell 26, 403–414 (2007).

    CAS  PubMed  Google Scholar 

  31. Mancias, J. D. & Goldberg, J. Structural basis of cargo membrane protein discrimination by the human COPII coat machinery. EMBO J. 27, 2918–2928 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  33. Sucic, S. et al. The serotonin transporter is an exclusive client of the coat protein complex II (COPII) component SEC24C. J. Biol. Chem. 286, 16482–16490 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Farhan, H. et al. Concentrative export from the endoplasmic reticulum of the gamma-aminobutyric acid transporter 1 requires binding to SEC24D. J. Biol. Chem. 282, 7679–7689 (2007).

    CAS  PubMed  Google Scholar 

  35. Merte, J. et al. Sec24b selectively sorts Vangl2 to regulate planar cell polarity during neural tube closure. Nat. Cell Biol. 12, 41–46 (2010).

    CAS  PubMed  Google Scholar 

  36. Wansleeben, C. et al. Planar cell polarity defects and defective Vangl2 trafficking in mutants for the COPII gene Sec24b. Development 137, 1067–1073 (2010).

    CAS  PubMed  Google Scholar 

  37. Zeuschner, D. et al. Immuno-electron tomography of ER exit sites reveals the existence of free COPII-coated transport carriers. Nat. Cell Biol. 8, 377–383 (2006).

    CAS  PubMed  Google Scholar 

  38. Appenzeller-Herzog, C. & Hauri, H. P. The ER-Golgi intermediate compartment (ERGIC): in search of its identity and function. J. Cell Sci. 119, 2173–2183 (2006).

    CAS  PubMed  Google Scholar 

  39. Novick, P., Field, C. & Schekman, R. Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway. Cell 21, 205–215 (1980).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  41. Watson, P., Townley, A. K., Koka, P., Palmer, K. J. & Stephens, D. J. Sec16 defines endoplasmic reticulum exit sites and is required for secretory cargo export in mammalian cells. Traffic 7, 1678–1687 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Iinuma, T. et al. Mammalian Sec16/p250 plays a role in membrane traffic from the endoplasmic reticulum. J. Biol. Chem. 282, 17632–17639 (2007).

    CAS  PubMed  Google Scholar 

  43. Bhattacharyya, D. & Glick, B. S. Two mammalian Sec16 homologues have nonredundant functions in endoplasmic reticulum (ER) export and transitional ER organization. Mol. Biol. Cell 18, 839–849 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Shindiapina, P. & Barlowe, C. Requirements for transitional endoplasmic reticulum site structure and function in Saccharomyces cerevisiae. Mol. Biol. Cell 21, 1530–1545 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Hughes, H. et al. Organisation of human ER-exit sites: requirements for the localisation of Sec16 to transitional ER. J. Cell Sci. 122, 2924–2934 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Ivan, V. et al. Drosophila Sec16 mediates the biogenesis of tER sites upstream of Sar1 through an arginine-rich motif. Mol. Biol. Cell 19, 4352–4365 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Espenshade, P., Gimeno, R. E., Holzmacher, E., Teung, P. & Kaiser, C. A. Yeast SEC16 gene encodes a multidomain vesicle coat protein that interacts with Sec23p. J. Cell Biol. 131, 311–324 (1995).

    CAS  PubMed  Google Scholar 

  48. Gimeno, R. E., Espenshade, P. & Kaiser, C. A. COPII coat subunit interactions: Sec24p and Sec23p bind to adjacent regions of Sec16p. Mol. Biol. Cell 7, 1815–1823 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Shaywitz, D. A., Espenshade, P. J., Gimeno, R. E. & Kaiser, C. A. COPII subunit interactions in the assembly of the vesicle coat. J. Biol. Chem. 272, 25413–25416 (1997).

    CAS  PubMed  Google Scholar 

  50. Whittle, J. R. & Schwartz, T. U. Structure of the Sec13-Sec16 edge element, a template for assembly of the COPII vesicle coat. J. Cell Biol. 190, 347–361 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Supek, F., Madden, D. T., Hamamoto, S., Orci, L. & Schekman, R. Sec16p potentiates the action of COPII proteins to bud transport vesicles. J. Cell Biol. 158, 1029–1038 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Hughes, H. & Stephens, D. J. Sec16A defines the site for vesicle budding from the endoplasmic reticulum on exit from mitosis. J. Cell Sci. 123, 4032–4038 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Witte, K. et al. TFG-1 function in protein secretion and oncogenesis. Nat. Cell Biol. 13, 550–558 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Yonekawa, S. et al. Sec16B is involved in the endoplasmic reticulum export of the peroxisomal membrane biogenesis factor peroxin 16 (Pex16) in mammalian cells. Proc. Natl Acad Sci USA 108, 12746–12751 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Pathre, P. et al. Activation of phospholipase D by the small GTPase Sar1p is required to support COPII assembly and ER export. EMBO J. 22, 4059–4069 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Blumental-Perry, A. et al. Phosphatidylinositol 4-phosphate formation at ER exit sites regulates ER export. Dev. Cell 11, 671–682 (2006).

    CAS  PubMed  Google Scholar 

  57. Shimoi, W. et al. p125 is localized in endoplasmic reticulum exit sites and involved in their organization. J. Biol. Chem. 280, 10141–10148 (2005).

    CAS  PubMed  Google Scholar 

  58. Ong, Y. S., Tang, B. L., Loo, L. S. & Hong, W. p125A exists as part of the mammalian Sec13/Sec31 COPII subcomplex to facilitate ER–Golgi transport. J. Cell Biol. 190, 331–345 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Farhan, H., Weiss, M., Tani, K., Kaufman, R. J. & Hauri, H. P. Adaptation of endoplasmic reticulum exit sites to acute and chronic increases in cargo load. EMBO J. 27, 2043–2054 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Presley, J. F. et al. ER-to-Golgi transport visualized in living cells. Nature 389, 81–85 (1997).

    CAS  PubMed  Google Scholar 

  61. Lippincott-Schwartz, J., Cole, N. B., Marotta, A., Conrad, P. A. & Bloom, G. S. Kinesin is the motor for microtubule-mediated Golgi-to-ER membrane traffic. J. Cell Biol. 128, 293–306 (1995).

    CAS  PubMed  Google Scholar 

  62. Scales, S. J., Pepperkok, R. & Kreis, T. E. Visualization of ER-to-Golgi transport in living cells reveals a sequential mode of action for COPII and COPI. Cell 90, 1137–1148 (1997).

    CAS  PubMed  Google Scholar 

  63. Hammond, A. T. & Glick, B. S. Dynamics of transitional endoplasmic reticulum sites in vertebrate cells. Mol. Biol. Cell 11, 3013–3030 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Watson, P., Forster, R., Palmer, K. J., Pepperkok, R. & Stephens, D. J. Coupling of ER exit to microtubules through direct interaction of COPII with dynactin. Nat. Cell Biol. 7, 48–55 (2005).

    CAS  PubMed  Google Scholar 

  65. Heinzer, S., Worz, S., Kalla, C., Rohr, K. & Weiss, M. A model for the self-organization of exit sites in the endoplasmic reticulum. J. Cell Sci. 121, 55–64 (2008).

    CAS  PubMed  Google Scholar 

  66. Srinivasan, R. et al. Nicotine up-regulates alpha4beta2 nicotinic receptors and ER exit sites via stoichiometry-dependent chaperoning. J. Gen. Physiol. 137, 59–79 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Farhan, H. et al. MAPK signaling to the early secretory pathway revealed by kinase/phosphatase functional screening. J. Cell Biol. 189, 997–1011 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Zacharogianni, M. et al. ERK7 is a negative regulator of protein secretion in response to amino-acid starvation by modulating Sec16 membrane association. EMBO J. 30, 3684–3700 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Aridor, M. & Fish, K. N. Selective targeting of ER exit sites supports axon development. Traffic 10, 1669–1684 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Kamiya, Y. et al. Molecular basis of sugar recognition by the human L-type lectins ERGIC-53, VIPL, and VIP36. J. Biol. Chem. 283, 1857–1861 (2008).

    CAS  PubMed  Google Scholar 

  71. Moussalli, M. et al. Mannose-dependent endoplasmic reticulum (ER)–Golgi intermediate compartment-53-mediated ER to Golgi trafficking of coagulation factors V and VIII. J. Biol. Chem. 274, 32539–32542 (1999).

    CAS  PubMed  Google Scholar 

  72. Zhang, B. et al. Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex. Nat. Genet. 34, 220–225 (2003).

    CAS  PubMed  Google Scholar 

  73. Nyfeler, B., Zhang, B., Ginsburg, D., Kaufman, R. J. & Hauri, H. P. Cargo selectivity of the ERGIC-53/MCFD2 transport receptor complex. Traffic 7, 1473–1481 (2006).

    CAS  PubMed  Google Scholar 

  74. Nyfeler, B. et al. Identification of ERGIC-53 as an intracellular transport receptor of alpha1-antitrypsin. J. Cell Biol. 180, 705–712 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Bonnon, C., Wendeler, M. W., Paccaud, J. P. & Hauri, H. P. Selective export of human GPI-anchored proteins from the endoplasmic reticulum. J. Cell Sci. 123, 1705–1715 (2010).

    CAS  PubMed  Google Scholar 

  76. Castillon, G. A. et al. The yeast p24 complex regulates GPI-anchored protein transport and quality control by monitoring anchor remodeling. Mol. Biol. Cell 22, 2924–2936 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Fujita, M. et al. Sorting of GPI-anchored proteins into ER exit sites by p24 proteins is dependent on remodeled GPI. J. Cell Biol. 194, 61–75 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Takida, S., Maeda, Y. & Kinoshita, T. Mammalian GPI-anchored proteins require p24 proteins for their efficient transport from the ER to the plasma membrane. Biochem. J. 409, 555–562 (2008).

    CAS  PubMed  Google Scholar 

  79. Springer, S. et al. The p24 proteins are not essential for vesicular transport in Saccharomyces cerevisiae. Proc. Natl Acad. Sci. USA 97, 4034–4039 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. Denzel, A. et al. The p24 family member p23 is required for early embryonic development. Curr. Biol. 10, 55–58 (2000).

    CAS  PubMed  Google Scholar 

  81. Lambert, G. et al. Control of cystic fibrosis transmembrane conductance regulator expression by BAP31. J. Biol. Chem. 276, 20340–20345 (2001).

    CAS  PubMed  Google Scholar 

  82. Abe, F., Van Prooyen, N., Ladasky, J. J. & Edidin, M. Interaction of Bap31 and MHC class I molecules and their traffic out of the endoplasmic reticulum. J. Immunol. 182, 4776–4783 (2009).

    CAS  PubMed  Google Scholar 

  83. Annaert, W. G., Becker, B., Kistner, U., Reth, M. & Jahn, R. Export of cellubrevin from the endoplasmic reticulum is controlled by BAP31. J. Cell Biol. 139, 1397–1410 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Brown, M. S. & Goldstein, J. L. Cholesterol feedback: from Schoenheimer's bottle to Scap's MELADL. J. Lipid Res. 50, Suppl. S15–S27 (2009).

    PubMed  PubMed Central  Google Scholar 

  85. Yang, T. et al. Crucial step in cholesterol homeostasis: sterols promote binding of SCAP to INSIG-1, a membrane protein that facilitates retention of SREBPs in ER. Cell 110, 489–500 (2002).

    CAS  PubMed  Google Scholar 

  86. Espenshade, P. J., Li, W. P. & Yabe, D. Sterols block binding of COPII proteins to SCAP, thereby controlling SCAP sorting in ER. Proc. Natl Acad. Sci. USA 99, 11694–11699 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Sun, L. P., Seemann, J., Goldstein, J. L. & Brown, M. S. Sterol-regulated transport of SREBPs from endoplasmic reticulum to Golgi: Insig renders sorting signal in Scap inaccessible to COPII proteins. Proc. Natl Acad. Sci. USA 104, 6519–6526 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. DeBose-Boyd, R. A. et al. Transport-dependent proteolysis of SREBP: relocation of site-1 protease from Golgi to ER obviates the need for SREBP transport to Golgi. Cell 99, 703–712 (1999).

    CAS  PubMed  Google Scholar 

  89. Kuwana, T., Peterson, P. A. & Karlsson, L. Exit of major histocompatibility complex class II-invariant chain p35 complexes from the endoplasmic reticulum is modulated by phosphorylation. Proc. Natl Acad. Sci. USA 95, 1056–1061 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. O'Kelly, I., Butler, M. H., Zilberberg, N. & Goldstein, S. A. Forward transport. 14-3-3 binding overcomes retention in endoplasmic reticulum by dibasic signals. Cell 111, 577–588 (2002).

    CAS  PubMed  Google Scholar 

  91. Chen, Y. T., Stewart, D. B. & Nelson, W. J. Coupling assembly of the E-cadherin/beta-catenin complex to efficient endoplasmic reticulum exit and basal-lateral membrane targeting of E-cadherin in polarized MDCK cells. J. Cell Biol. 144, 687–699 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Nakamura, T. et al. PX-RICS mediates ER-to-Golgi transport of the N-cadherin/beta-catenin complex. Genes Dev. 22, 1244–1256 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Wang, J. et al. Dishevelled genes mediate a conserved mammalian PCP pathway to regulate convergent extension during neurulation. Development 133, 1767–1778 (2006).

    CAS  PubMed  Google Scholar 

  94. Simons, M. et al. Electrochemical cues regulate assembly of the Frizzled/Dishevelled complex at the plasma membrane during planar epithelial polarization. Nat. Cell Biol. 11, 286–294 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Das, S. et al. ERp29 restricts Connexin43 oligomerization in the endoplasmic reticulum. Mol. Biol. Cell 20, 2593–2604 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Aryal, R. P., Ju, T. & Cummings, R. D. The endoplasmic reticulum chaperone Cosmc directly promotes in vitro folding of T-synthase. J. Biol. Chem. 285, 2456–2462 (2010).

    CAS  PubMed  Google Scholar 

  97. Schindler, A. J. & Schekman, R. In vitro reconstitution of ER-stress induced ATF6 transport in COPII vesicles. Proc. Natl Acad. Sci. USA 106, 17775–17780 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Shen, J., Chen, X., Hendershot, L. & Prywes, R. ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals. Dev. Cell 3, 99–111 (2002).

    CAS  PubMed  Google Scholar 

  99. Saito, K. et al. TANGO1 facilitates cargo loading at endoplasmic reticulum exit sites. Cell 136, 891–902 (2009).

    CAS  PubMed  Google Scholar 

  100. Bachinger, H. P., Doege, K. J., Petschek, J. P., Fessler, L. I. & Fessler, J. H. Structural implications from an electronmicroscopic comparison of procollagen V with procollagen I, pC-collagen I, procollagen IV, and a Drosophila procollagen. J. Biol. Chem. 257, 14590–14592 (1982).

    CAS  PubMed  Google Scholar 

  101. Zilversmit, D. B. Formation and transport of chylomicrons. Fed. Proc. 26, 1599–1605 (1967).

    CAS  PubMed  Google Scholar 

  102. Aridor, M., Bannykh, S. I., Rowe, T. & Balch, W. E. Sequential coupling between COPII and COPI vesicle coats in endoplasmic reticulum to Golgi transport. J. Cell Biol. 131, 875–893 (1995).

    CAS  PubMed  Google Scholar 

  103. Bonfanti, L. et al. Procollagen traverses the Golgi stack without leaving the lumen of cisternae: evidence for cisternal maturation. Cell 95, 993–1003 (1998).

    CAS  PubMed  Google Scholar 

  104. Townley, A. K. et al. Efficient coupling of Sec23–Sec24 to Sec13–Sec31 drives COPII-dependent collagen secretion and is essential for normal craniofacial development. J. Cell Sci. 121, 3025–3034 (2008).

    CAS  PubMed  Google Scholar 

  105. Wilson, D. G. et al. Global defects in collagen secretion in a Mia3/TANGO1 knockout mouse. J. Cell Biol. 193, 935–951 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Saito, K. et al. cTAGE5 mediates collagen secretion through interaction with TANGO1 at endoplasmic reticulum exit sites. Mol. Biol. Cell 22, 2301–2308 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Malhotra, V. & Erlmann, P. Protein export at the ER: loading big collagens into COPII carriers. EMBO J. 30, 3475–3480 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Boyadjiev, S. A. et al. A novel dysmorphic syndrome with open calvarial sutures and sutural cataracts maps to chromosome 14q13–q21. Hum. Genet. 113, 1–9 (2003).

    CAS  PubMed  Google Scholar 

  109. Boyadjiev, S. A. et al. Cranio-lenticulo-sutural dysplasia is caused by a SEC23A mutation leading to abnormal endoplasmic-reticulum-to-Golgi trafficking. Nat. Genet. 38, 1192–1197 (2006).

    CAS  PubMed  Google Scholar 

  110. Saito, A. et al. Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis. Nat. Cell Biol. 11, 1197–1204 (2009).

    CAS  PubMed  Google Scholar 

  111. 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).

    CAS  PubMed  Google Scholar 

  112. Jones, B. et al. Mutations in a Sar1 GTPase of COPII vesicles are associated with lipid absorption disorders. Nat. Genet. 34, 29–31 (2003).

    CAS  PubMed  Google Scholar 

  113. Treepongkaruna, S. et al. Novel missense mutations of SAR1B gene in an infant with chylomicron retention disease. J. Pediatr. Gastroenterol. Nutr. 48, 370–373 (2009).

    PubMed  Google Scholar 

  114. Silvain, M. et al. Anderson's disease (chylomicron retention disease): a new mutation in the SARA2 gene associated with muscular and cardiac abnormalities. Clin. Genet. 74, 546–552 (2008).

    CAS  PubMed  Google Scholar 

  115. Levy, E. et al. Expression of Sar1b enhances chylomicron assembly and key components of the coat protein complex ii system driving vesicle budding. Arterioscler. Thromb. Vasc. Biol. 31, 2692–2699 (2011).

    CAS  PubMed  Google Scholar 

  116. Siddiqi, S. A., Gorelick, F. S., Mahan, J. T. & Mansbach, C. M. II COPII proteins are required for Golgi fusion but not for endoplasmic reticulum budding of the pre-chylomicron transport vesicle. J. Cell Sci. 116, 415–427 (2003).

    CAS  PubMed  Google Scholar 

  117. Siddiqi, S. et al. A novel multiprotein complex is required to generate the prechylomicron transport vesicle from intestinal ER. J. Lipid Res. 51, 1918–1928 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Siddiqi, S., Siddiqi, S. A. & Mansbach, C. M. II Sec24C is required for docking the prechylomicron transport vesicle with the Golgi. J. Lipid Res. 51, 1093–1100 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Bacia, K. et al. Multibudded tubules formed by COPII on artificial liposomes. Sci. Rep. 1, 17 (2011).

    PubMed  PubMed Central  Google Scholar 

  120. O'Donnell, J., Maddox, K. & Stagg, S. The structure of a COPII tubule. J. Struct. Biol. 173, 358–364 (2011).

    CAS  PubMed  Google Scholar 

  121. Kim, W. et al. Systematic and quantitative assessment of the ubiquitin-modified proteome. Mol. Cell 44, 325–340 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. la Cour, J. M., Mollerup, J. & Berchtold, M. W. ALG-2 oscillates in subcellular localization, unitemporally with calcium oscillations. Biochem. Biophys. Res. Commun. 353, 1063–1067 (2007).

    CAS  PubMed  Google Scholar 

  123. Yamasaki, A., Tani, K., Yamamoto, A., Kitamura, N. & Komada, M. The Ca2+-binding protein ALG-2 is recruited to endoplasmic reticulum exit sites by Sec31A and stabilizes the localization of Sec31A. Mol. Biol. Cell 17, 4876–4887 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Bentley, M. et al. Vesicular calcium regulates coat retention, fusogenicity, and size of pre-Golgi intermediates. Mol. Biol. Cell 21, 1033–1046 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Shibata, H. et al. The ALG-2 binding site in Sec31A influences the retention kinetics of Sec31A at the endoplasmic reticulum exit sites as revealed by live-cell time-lapse imaging. Biosci. Biotechnol. Biochem. 74, 1819–1826 (2010).

    CAS  PubMed  Google Scholar 

  126. Shibata, H., Suzuki, H., Yoshida, H. & Maki, M. ALG-2 directly binds Sec31A and localizes at endoplasmic reticulum exit sites in a Ca2+-dependent manner. Biochem. Biophys. Res. Commun. 353, 756–763 (2007).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank S. K. Lam, A. Fernandes and J. McKenzie for critical reading of the manuscript and discussions. G.Z. and K.B.P. are Human Frontier Science Program postdoctoral fellows. R.S. is a Senior Fellow of the UC Berkeley Miller Institute and is supported as an Investigator of the Howard Hughes Medical Institute.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Randy Schekman.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zanetti, G., Pahuja, K., Studer, S. et al. COPII and the regulation of protein sorting in mammals. Nat Cell Biol 14, 20–28 (2012). https://doi.org/10.1038/ncb2390

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb2390

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