Antonie van Leeuwenhoek

, Volume 61, Issue 2, pp 123–131 | Cite as

The receptor-mediated retention of resident proteins in the endoplasmic reticulum

  • David J. Vaux
  • Stephen D. Fuller


Overwhelming evidence has accumulated to support the bulk flow hypothesis which states that proteins entering the exocytic pathway will follow a default route to the plasma membrane unless they carry specific signals for receptor mediated diversion. The resident soluble and membrane proteins of the ER present a clear example of this signal mediated exception to bulk flow. Their study also provides insights relevant to retention or targetting signals operating later in the secretory pathway.

The last few years have seen enormous progress in this field, in the delineation of the retention problem, the identification of the retention signal and recently in the identification of components of the retention machinery itself. The next few years hold the promise of a more complete understanding of the retention machinery and of the enigmatic cellular compartment in which it functions.

Key words

KDEL receptor salvage compartment retention signals S. cerevisiae mammalian cells 


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  1. Booth C & Koch GL (1989) Perturbation of cellular calcium induces secretion of luminal ER proteins: Cell 59: 729–37Google Scholar
  2. Ceriotti A & Colman A (1988) Binding to membrane proteins within the endoplasmic reticulum cannot explain the retention of the glucose-regulated protein GRP78 in Xenopus oocytes: EMBO J. 7: 633–8Google Scholar
  3. Dean N & Pelham HR (1990) Recycling of proteins from the Golgi compartment to the ER in yeast J. Cell Biol. 111: 369–77Google Scholar
  4. Freedman RB (1984) Native disulphide bond formation in protein biosynthesis: evidence ofr the rolde of protein disulphide isomerase. Trends Biochem. Sci. 9: 438–441Google Scholar
  5. Haas I & Wabl M (1983) Immunoglobulin heavy chain binding protein. Nature 306: 387–389Google Scholar
  6. Hardwick KG, Lewis MJ, Semenza J, Dean N & Pelham HR (1990). ERDI, a yeast gene required for the retention of luminal endoplasmic reticulum proteins, affects glycoprotein processing in the Golgi apparatus. EMBO J. 9: 623–30Google Scholar
  7. Howell KE, Kern H, Fuller SD & Tooze J (1988) Sorting and coordinate induction of three endoplasmic reticulum proteins containing the KDEL retention signal. J. Cell Biol. 107: 772aGoogle Scholar
  8. Hurtley SM & Helenius A (1989) Protein oligomerization in the endoplasmic reticulum. Ann. Rev Cell Biol. 5: 277–307Google Scholar
  9. Inohara N, Shimomura S, Fukui T & Futai M (1989) Auxinbinding protein located in the endoplasmic reticulum of maize shoots: molecular cloning and complete primary structure. Proc Natl Acad Sci USA 86: 3564–8Google Scholar
  10. Jackson MR, Nilsson T & Peterson PA (1990) Identification of a consensus motif for the retention of transmembrane proteins in the endoplasmic reticulum. EMBO J. 9: 3153–3162Google Scholar
  11. Jerne NK (1974) Towards a network theory of the immune system. Ann. Immunol. (Inst. Pasteur). 125C: 373Google Scholar
  12. (1985) The generative grammar of the immune system. EMBO J. 4: 847–852Google Scholar
  13. Kelly RB (1990) Tracking an elusive receptor. Nature 345: 480–1Google Scholar
  14. Kivirikko KI, Myllyla R & Pihlajaniemi T (1989) Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit. Faseb. J. 3: 1609–17Google Scholar
  15. Kuroki K, Russnak R & Ganem D (1989) Novel N-terminal amino acid sequence required for retention of a hepatitis B virus glycoprotein in the endoplasmic reticulum. Mol. Cell. Biol. 9: 4459–66Google Scholar
  16. Lewis MJ & Pelham HRB (1990) A human homologue of the yeast HDEL receptor. Nature 348: 162–163Google Scholar
  17. Lewis MJ, Sweet DJ & Pelham HR (1990) The ERD2 gene determines the specificity of the luminal ER protein retention system. Cell 61: 1359–63Google Scholar
  18. Mazzarella RA, Srinivasan M, Haugejorden SM & Green M (1990) ERp72, an abundant luminal endoplasmic reticulum protein, contains three copies of the active site sequences of protein disulfide isomerase. J. Biol. Chem. 265: 1094–101Google Scholar
  19. Munro S & Pelham HR (1987) A C-terminal signal prevents secretion of luminal ER proteins. Cell. 48: 899–907Google Scholar
  20. (1987) An hsp70-like protein in the ER: identity with the 78 kD glucose regulated protein and immunoglobulin heavy chain binding protein. Cell. 46: 291–300Google Scholar
  21. Murakami H, Blobel G & Pain D (1990). Isolation and characterization of the gene for a yeast mitochondrial import receptor. Nature 347: 488–491Google Scholar
  22. Nilsson T, Jackson M & Peterson PA (1989) Short cytoplasmic sequences serve as retention signals for transmembrane proteins in the endoplasmic reticulum. Cell 58: 707–18Google Scholar
  23. Paabo S, Bhat BM, Wold WS & Peterson PA (1987) A short sequence in the COOH-terminus makes an adenovirus membrane glycoprotein a resident of the endoplasmic reticulum. Cell 50: 311–7Google Scholar
  24. Pelham HR (1989) Control of protein exit from the endoplasmic reticulum. Annu. Rev. Cell Biol. 5: 1–23Google Scholar
  25. (1988) Evidence that luminal ER proteins are sorted from secreted proteins in a post-ER compartment. EMBO J. 7: 913–918Google Scholar
  26. (1990) The retention signal for soluble proteins of the endoplasmic reticulum. Trends Biochem. Sci. 15: 483–486Google Scholar
  27. Pelham HRB, Hardwick KG & Lewis MJ (1988) Sorting of soluble ER proteins in yeast. EMBO J. 7: 1757–1762Google Scholar
  28. Perelson AS (1989) Immune network theory. Immun. Rev. 110 (September): 5–36Google Scholar
  29. Poruchynsky MS & Atkinson PH (1988) Primary sequence domains required for the retention of rotavirus VP7 in the endoplasmic reticulum. J. Cell Biol. 107: 1697–706Google Scholar
  30. Rose JK & Doms RW (1988) Regulation of protein export from the endoplasmic reticulum. Ann. Rev. Cell Biol. 4: 257–288Google Scholar
  31. Saraste J & Kuismanen E (1984) Pre- and post-Golgi vacuoles operate in the transport of Semliki forest virus membrane glcoproteins to the cell surface. Cell 38: 535–549Google Scholar
  32. Schweizer A, Matter K, Ketcham CA & Hauri H-P (1991) The Isolated ER-Golgi Intermediate Compartment Exhibits Properties That Are From ER and cis-Golgi. J. Cell Biol. 113: 45–54Google Scholar
  33. Semenza JC, Hardwick KG, Dean N & Pelham HR (1990) ERD2, a yeast gene required for the receptor-mediated retrieval of luminal ER proteins from the secretory pathway. Cell 61: 1349–57Google Scholar
  34. Tooze J, Kern HF, Fuller SD & Howell KE (1989) Condensation-sorting events in the rough endoplasmic reticulum of exocrine pancreatic cells. J. Cell Biol. 109: 35–50Google Scholar
  35. Vaux D, Tooze J & Fuller S (1990) Identification by antiidiotype antibodies of an intracellular membrane protein that recognizes a mammalian endoplasmic reticulum retention signal [see comments] [Comment in: Nature (1990) Jun 7: 345: 480–1] Nature 345: 495–502Google Scholar
  36. Vaux DJ & Fuller SD (1991) The use of anti-idiotype antibodies for the characterization of protein-protein interactions. Methods in Cell Biology. (in press)Google Scholar
  37. Warren G (1987) Signals and Salvage Sequences. Nature (Lond.) 327: 17–18Google Scholar
  38. Wieland FT, Gleason ML, Serafini TA & Rothman JE (1987) The rate of bulk flow from the endoplasmic reticulum to the cell surface. Cell 50: 289–300Google Scholar
  39. Yoshimori T, Semba T, Takemoto H, Akagi S, Yamamoto A & Tashiro Y (1990) Protein disulfide-isomerase in rat exocrine pancreatic cells is exported from the endoplasmic reticulum despite possessing the retention signal. J. Biol. Chem. 265: 15984–90Google Scholar
  40. Zagouras P & Rose JK (1989) Carboxy-terminal SEKDEL sequences retard but do not retain two secretory proteins in the endoplasmic reticulum. J. Cell. Biol. 109: 2633–2640Google Scholar

Copyright information

© Kluwer Academic Publishers 1992

Authors and Affiliations

  • David J. Vaux
    • 1
    • 2
  • Stephen D. Fuller
    • 1
    • 2
  1. 1.The Cell Biology ProgrammeEuropean Molecular Biology LaboratoryHeidelbergGermany
  2. 2.The Biological Structures and Biocomputing ProgrammeEuropean Molecular Biology LaboratoryHeidelbergGermany

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