Skip to main content
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1993 Jan 2;120(2):325–328. doi: 10.1083/jcb.120.2.325

Molecular cloning, characterization, subcellular localization and dynamics of p23, the mammalian KDEL receptor

PMCID: PMC2119513  PMID: 8380600

Abstract

We have isolated a cDNA clone (mERD2) for the mammalian (bovine) homologue of the yeast ERD2 gene, which codes for the yeast HDEL receptor. The deduced amino acid sequence bears extensive homology to its yeast counterpart and is almost identical to a previously described human sequence. The sequence predicts a very hydrophobic protein with multiple membrane spanning domains, as confirmed by analysis of the in vitro translation product. The protein encoded by mERD2 (p23) has widespread occurrence, being present in all the cell types examined. p23 was localized to the cis-side of the Golgi apparatus and to a spotty intermediate compartment which mediates ER to Golgi transport. A majority of the intracellular staining could be accumulated in the intermediate compartment by a low temperature (15 degrees C) or brefeldin A. During recovery from these treatments, the spotty intermediate compartment staining of p23 was shifted to the perinuclear staining of the Golgi apparatus and tubular structures marked by p23 were observed. These tubular structures may serve to mediate transport between the intermediate compartment and the Golgi apparatus.

Full Text

The Full Text of this article is available as a PDF (6.7 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alcalde J., Bonay P., Roa A., Vilaro S., Sandoval I. V. Assembly and disassembly of the Golgi complex: two processes arranged in a cis-trans direction. J Cell Biol. 1992 Jan;116(1):69–83. doi: 10.1083/jcb.116.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bonatti S., Migliaccio G., Simons K. Palmitylation of viral membrane glycoproteins takes place after exit from the endoplasmic reticulum. J Biol Chem. 1989 Jul 25;264(21):12590–12595. [PubMed] [Google Scholar]
  3. Brown W. J., Farquhar M. G. Immunoperoxidase methods for the localization of antigens in cultured cells and tissue sections by electron microscopy. Methods Cell Biol. 1989;31:553–569. doi: 10.1016/s0091-679x(08)61626-x. [DOI] [PubMed] [Google Scholar]
  4. Hong W. J., Doyle D. Molecular dissection of the NH2-terminal signal/anchor sequence of rat dipeptidyl peptidase IV. J Cell Biol. 1990 Aug;111(2):323–328. doi: 10.1083/jcb.111.2.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hsu V. W., Shah N., Klausner R. D. A brefeldin A-like phenotype is induced by the overexpression of a human ERD-2-like protein, ELP-1. Cell. 1992 May 15;69(4):625–635. doi: 10.1016/0092-8674(92)90226-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hsu V. W., Yuan L. C., Nuchtern J. G., Lippincott-Schwartz J., Hammerling G. J., Klausner R. D. A recycling pathway between the endoplasmic reticulum and the Golgi apparatus for retention of unassembled MHC class I molecules. Nature. 1991 Aug 1;352(6334):441–444. doi: 10.1038/352441a0. [DOI] [PubMed] [Google Scholar]
  7. Hunziker W., Whitney J. A., Mellman I. Selective inhibition of transcytosis by brefeldin A in MDCK cells. Cell. 1991 Nov 1;67(3):617–627. doi: 10.1016/0092-8674(91)90535-7. [DOI] [PubMed] [Google Scholar]
  8. Klausner R. D., Donaldson J. G., Lippincott-Schwartz J. Brefeldin A: insights into the control of membrane traffic and organelle structure. J Cell Biol. 1992 Mar;116(5):1071–1080. doi: 10.1083/jcb.116.5.1071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kornfeld R., Kornfeld S. Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem. 1985;54:631–664. doi: 10.1146/annurev.bi.54.070185.003215. [DOI] [PubMed] [Google Scholar]
  10. Lewis M. J., Pelham H. R. A human homologue of the yeast HDEL receptor. Nature. 1990 Nov 8;348(6297):162–163. doi: 10.1038/348162a0. [DOI] [PubMed] [Google Scholar]
  11. Lewis M. J., Pelham H. R. Ligand-induced redistribution of a human KDEL receptor from the Golgi complex to the endoplasmic reticulum. Cell. 1992 Jan 24;68(2):353–364. doi: 10.1016/0092-8674(92)90476-s. [DOI] [PubMed] [Google Scholar]
  12. Lewis M. J., Sweet D. J., Pelham H. R. The ERD2 gene determines the specificity of the luminal ER protein retention system. Cell. 1990 Jun 29;61(7):1359–1363. doi: 10.1016/0092-8674(90)90699-f. [DOI] [PubMed] [Google Scholar]
  13. Lippincott-Schwartz J., Donaldson J. G., Schweizer A., Berger E. G., Hauri H. P., Yuan L. C., Klausner R. D. Microtubule-dependent retrograde transport of proteins into the ER in the presence of brefeldin A suggests an ER recycling pathway. Cell. 1990 Mar 9;60(5):821–836. doi: 10.1016/0092-8674(90)90096-w. [DOI] [PubMed] [Google Scholar]
  14. Lippincott-Schwartz J., Yuan L., Tipper C., Amherdt M., Orci L., Klausner R. D. Brefeldin A's effects on endosomes, lysosomes, and the TGN suggest a general mechanism for regulating organelle structure and membrane traffic. Cell. 1991 Nov 1;67(3):601–616. doi: 10.1016/0092-8674(91)90534-6. [DOI] [PubMed] [Google Scholar]
  15. Lodish H. F., Kong N., Hirani S., Rasmussen J. A vesicular intermediate in the transport of hepatoma secretory proteins from the rough endoplasmic reticulum to the Golgi complex. J Cell Biol. 1987 Feb;104(2):221–230. doi: 10.1083/jcb.104.2.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Louvard D., Reggio H., Warren G. Antibodies to the Golgi complex and the rough endoplasmic reticulum. J Cell Biol. 1982 Jan;92(1):92–107. doi: 10.1083/jcb.92.1.92. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Low S. H., Wong S. H., Tang B. L., Hong W. J. Involvement of both vectorial and transcytotic pathways in the preferential apical cell surface localization of rat dipeptidyl peptidase IV in transfected LLC-PK1 cells. J Biol Chem. 1991 Oct 15;266(29):19710–19716. [PubMed] [Google Scholar]
  18. Munro S., Pelham H. R. A C-terminal signal prevents secretion of luminal ER proteins. Cell. 1987 Mar 13;48(5):899–907. doi: 10.1016/0092-8674(87)90086-9. [DOI] [PubMed] [Google Scholar]
  19. Orci L., Tagaya M., Amherdt M., Perrelet A., Donaldson J. G., Lippincott-Schwartz J., Klausner R. D., Rothman J. E. Brefeldin A, a drug that blocks secretion, prevents the assembly of non-clathrin-coated buds on Golgi cisternae. Cell. 1991 Mar 22;64(6):1183–1195. doi: 10.1016/0092-8674(91)90273-2. [DOI] [PubMed] [Google Scholar]
  20. Pelham H. R. Evidence that luminal ER proteins are sorted from secreted proteins in a post-ER compartment. EMBO J. 1988 Apr;7(4):913–918. doi: 10.1002/j.1460-2075.1988.tb02896.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pelham H. R. The retention signal for soluble proteins of the endoplasmic reticulum. Trends Biochem Sci. 1990 Dec;15(12):483–486. doi: 10.1016/0968-0004(90)90303-s. [DOI] [PubMed] [Google Scholar]
  22. Ridgway N. D., Dawson P. A., Ho Y. K., Brown M. S., Goldstein J. L. Translocation of oxysterol binding protein to Golgi apparatus triggered by ligand binding. J Cell Biol. 1992 Jan;116(2):307–319. doi: 10.1083/jcb.116.2.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Russ G., Bennink J. R., Bächi T., Yewdell J. W. Influenza virus hemagglutinin trimers and monomers maintain distinct biochemical modifications and intracellular distribution in brefeldin A-treated cells. Cell Regul. 1991 Jul;2(7):549–563. doi: 10.1091/mbc.2.7.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Saraste J., Kuismanen E. Pre- and post-Golgi vacuoles operate in the transport of Semliki Forest virus membrane glycoproteins to the cell surface. Cell. 1984 Sep;38(2):535–549. doi: 10.1016/0092-8674(84)90508-7. [DOI] [PubMed] [Google Scholar]
  25. Saraste J., Palade G. E., Farquhar M. G. Antibodies to rat pancreas Golgi subfractions: identification of a 58-kD cis-Golgi protein. J Cell Biol. 1987 Nov;105(5):2021–2029. doi: 10.1083/jcb.105.5.2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Saraste J., Svensson K. Distribution of the intermediate elements operating in ER to Golgi transport. J Cell Sci. 1991 Nov;100(Pt 3):415–430. doi: 10.1242/jcs.100.3.415. [DOI] [PubMed] [Google Scholar]
  27. Schweizer A., Fransen J. A., Bächi T., Ginsel L., Hauri H. P. Identification, by a monoclonal antibody, of a 53-kD protein associated with a tubulo-vesicular compartment at the cis-side of the Golgi apparatus. J Cell Biol. 1988 Nov;107(5):1643–1653. doi: 10.1083/jcb.107.5.1643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schweizer A., Matter K., Ketcham C. M., Hauri H. P. The isolated ER-Golgi intermediate compartment exhibits properties that are different from ER and cis-Golgi. J Cell Biol. 1991 Apr;113(1):45–54. doi: 10.1083/jcb.113.1.45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Semenza J. C., Hardwick K. G., Dean N., Pelham H. R. ERD2, a yeast gene required for the receptor-mediated retrieval of luminal ER proteins from the secretory pathway. Cell. 1990 Jun 29;61(7):1349–1357. doi: 10.1016/0092-8674(90)90698-e. [DOI] [PubMed] [Google Scholar]
  30. Tang B. L., Wong S. H., Low S. H., Hong W. Retention of a type II surface membrane protein in the endoplasmic reticulum by the Lys-Asp-Glu-Leu sequence. J Biol Chem. 1992 Apr 5;267(10):7072–7076. [PubMed] [Google Scholar]
  31. Vaux D., Tooze J., Fuller S. Identification by anti-idiotype antibodies of an intracellular membrane protein that recognizes a mammalian endoplasmic reticulum retention signal. Nature. 1990 Jun 7;345(6275):495–502. doi: 10.1038/345495a0. [DOI] [PubMed] [Google Scholar]
  32. Wood S. A., Park J. E., Brown W. J. Brefeldin A causes a microtubule-mediated fusion of the trans-Golgi network and early endosomes. Cell. 1991 Nov 1;67(3):591–600. doi: 10.1016/0092-8674(91)90533-5. [DOI] [PubMed] [Google Scholar]
  33. Yuan L., Barriocanal J. G., Bonifacino J. S., Sandoval I. V. Two integral membrane proteins located in the cis-middle and trans-part of the Golgi system acquire sialylated N-linked carbohydrates and display different turnovers and sensitivity to cAMP-dependent phosphorylation. J Cell Biol. 1987 Jul;105(1):215–227. doi: 10.1083/jcb.105.1.215. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES