A molecular specificity code for the three mammalian KDEL receptors
Open accessAbstract
AC-terminal KDEL-like motif prevents secretion of soluble endoplasmic reticulum (ER)–resident proteins. This motif interacts with KDEL receptors localized in the intermediate compartment and Golgi apparatus. Such binding triggers retrieval back to the ER via a coat protein I–dependent pathway. To date, two human KDEL receptors have been reported. Here, we report the Golgi localization of a third human KDEL receptor. Using a reporter construct system from a screen of 152 variants, we identified 35 KDEL-like variants that result in efficient ER localization but do not match the current Prosite motif for ER localization ([KRHQSA]-[DENQ]-E-L). We cloned 16 human proteins with one of these motifs and all were found in the ER. A subsequent screen by bimolecular fluorescence complementation determined the specificities of the three human KDEL receptors. Each KDEL receptor has a unique pattern of motifs with which it interacts. This suggests a specificity in the retrieval of human proteins that contain different KDEL variants.
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FKBP14 encodes FKBP22, a peptidyl-prolyl cis-trans isomerase localized in the ER lumen that interacts with different types of COLLs and catalyzes cis-trans-isomerization of peptide bonds, promoting COLLIII folding.
“FKBP14 encodes FKBP22, a peptidyl-prolyl cis-trans isomerase localized in the ER lumen [41] that interacts with different types of COLLs, i.e., COLLIII, COLLVI, and COLLX, and during COLLs triple helix formation catalyzes cis–trans-isomerization of peptide bonds, promoting in particular the COLLIII folding [39,42].”
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Cites
Improved Prediction of Signal Peptides: SignalP 3.0
Dyrløv Bendtsen, J., Nielsen, H., von Heijne, G., & Brunak, S. (2004) · Journal of Molecular Biology · doi:10.1016/j.jmb.2004.05.028 · Cited by 6,350 · see citing works
Setting the Standards: Quality Control in the Secretory Pathway
Ellgaard, L., Molinari, M., & Helenius, A. (1999) · Science · doi:10.1126/science.286.5446.1882 · Cited by 1,192 · see citing works
Reducing the Environmental Sensitivity of Yellow Fluorescent Protein
Griesbeck, O., Baird, G. S., Campbell, R. E., Zacharias, D. A., & Tsien, R. Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102815200 · Cited by 1,023 · see citing works
Hulo, N. (2005) · Nucleic Acids Research · doi:10.1093/nar/gkj063 · Cited by 971 · see citing works
The human protein disulphide isomerase family: substrate interactions and functional properties
Ellgaard, L., & Ruddock, L. W. (2005) · EMBO Reports · doi:10.1038/sj.embor.7400311 · Cited by 757 · see citing works
Self-citationSemenza, J. C., Hardwick, K., Dean, N., & Pelham, H. R. B. (1990) · Cell · doi:10.1016/0092-8674(90)90698-e · Cited by 539 · see citing works
Meunier, L., Usherwood, Y.-K., Chung, K. T., & Hendershot, L. M. (2002) · Molecular Biology of the Cell · doi:10.1091/mbc.e02-05-0311 · Cited by 530 · see citing works
Rebhan, M., Caspi, V. C., Prilusky, J., & Lancet, D. (1998) · Bioinformatics · doi:10.1093/bioinformatics/14.8.656 · Cited by 502 · see citing works
Better prediction of protein cellular localization sites with the k nearest neighbors classifier.
Horton, P., & Nakai, K. (1997) · PubMed · Cited by 439 · see citing works
Lewis, M., & Pelham, H. R. B. (1992) · Cell · doi:10.1016/0092-8674(92)90476-s · Cited by 402 · see citing works
Interaction of the Thiol-Dependent Reductase ERp57 with Nascent Glycoproteins
Oliver, J. D., van der Wal, F. J., Bulleid, N. J., & High, S. (1997) · Science · doi:10.1126/science.275.5296.86 · Cited by 390 · see citing works
Zapun, A., Darby, N. J., Tessier, D. C., Michalak, M., Bergeron, J. J. M., & Thomas, D. Y. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.11.6009 · Cited by 336 · see citing works
A human homologue of the yeast HDEL receptor
Lewis, M., & Pelham, H. R. B. (1990) · Nature · doi:10.1038/348162a0 · Cited by 335 · see citing works
ERp44, a novel endoplasmic reticulum folding assistant of the thioredoxin family
Anelli, T., Alessio, M., Mezghrani, A., Simmen, T., Talamo, F., Bachi, A., & Sitia, R. (2002) · The EMBO Journal · doi:10.1093/emboj/21.4.835 · Cited by 273 · see citing works
Sorting of soluble ER proteins in yeast.
Pelham, H. R. B., Hardwick, K., & Lewis, M. J. (1988) · The EMBO Journal · doi:10.1002/j.1460-2075.1988.tb03005.x · Cited by 269 · see citing works
The ERD2 gene determines the specificity of the luminal ER protein retention system
Lewis, M. J., Sweet, D. J., & Pelham, H. R. B. (1990) · Cell · doi:10.1016/0092-8674(90)90699-f · Cited by 238 · see citing works
Chalkley, R. J., Baker, P. R., Huang, L., Hansen, K. C., Allen, N. P. C., Rexach, M. F., & Burlingame, A. L. (2005) · Molecular & Cellular Proteomics · doi:10.1074/mcp.d500002-mcp200 · Cited by 179 · see citing works
Capturing protein interactions in the secretory pathway of living cells
Nyfeler, B., Michnick, S. W., & Hauri, H. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501976102 · Cited by 177 · see citing works
Vuori, K. A. M., Pihlajaniemi, T. A., Myllylä, R., & Kivirikko, K. I. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05515.x · Cited by 154 · see citing works
Townsley, F. M., Wilson, D. W., & Pelham, H. R. B. (1993) · The EMBO Journal · doi:10.1002/j.1460-2075.1993.tb05943.x · Cited by 148 · see citing works
Genes that allow yeast cells to grow in the absence of the HDEL receptor.
Hardwick, K., Boothroyd, J. C., Rudner, A. D., et al. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05512.x · Cited by 113 · see citing works
The Dynamic Organisation of the Secretory Pathway.
Pelham, H. R. B. (1996) · Cell Structure and Function · doi:10.1247/csf.21.413 · Cited by 110 · see citing works
Alanen, H. I., Williamson, R. A., Howard, M. J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304598200 · Cited by 100 · see citing works
Self-citationSequence of a second human KDEL receptor
Lewis, M., & Pelham, H. R. B. (1992) · Journal of Molecular Biology · doi:10.1016/0022-2836(92)91039-r · Cited by 90 · see citing works
Chalkley, R. J., Baker, P. R., Hansen, K. C., et al. (2005) · Molecular & Cellular Proteomics · doi:10.1074/mcp.d500001-mcp200 · Cited by 89 · see citing works
Sweet, D. J., & Pelham, H. R. B. (1992) · The EMBO Journal · doi:10.1002/j.1460-2075.1992.tb05071.x · Cited by 89 · see citing works
Defining the Domain Boundaries of the Human Protein Disulfide Isomerases
Alanen, H. I., Salo, K. E. H., Pekkala, M., Siekkinen, H. M., Pirneskoski, A., & Ruddock, L. W. (2003) · Antioxidants and Redox Signaling · doi:10.1089/152308603768295096 · Cited by 78 · see citing works
Self-citationThe structure in solution of the b domain of protein disulfide isomerase*
Kemmink, J., Dijkstra, K., Mariani, M., Scheek, R. M., Penka, E., Nilges, M., & Darby, N. J. (1999) · Journal of Biomolecular NMR · doi:10.1023/a:1008341820489 · Cited by 70 · see citing works
Alanen, H. I., Williamson, R. A., Howard, M. J., Hatahet, F., Salo, K. E. H., Kauppila, A., Kellokumpu, S., & Ruddock, L. W. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604314200 · Cited by 56 · see citing works
Self-citationChanging the specificity of the sorting receptor for luminal endoplasmic reticulum proteins
Semenza, J. C., & Pelham, H. R. B. (1992) · Journal of Molecular Biology · doi:10.1016/0022-2836(92)90571-z · Cited by 25 · see citing works
Anson, D. S., & Bielicki, J. (1999) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(98)00148-4 · Cited by 10 · see citing works
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Baumann, M., Giunta, C., Krabichler, B., Rüschendorf, F., Zoppi, N., Colombi, M., Bittner, R. E., Quijano-Roy, S., Muntoni, F., Cirak, S., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.12.004 · Cited by 162 · see citing works
Chiarelli, N., Carini, G., Zoppi, N., Ritelli, M., & Colombi, M. (2018) · PLOS ONE · doi:10.1371/journal.pone.0191220 · Cited by 45 · see citing works
- Authors
- Raykhel, I., Alanen, H., Salo, K., Jurvansuu, J., Nguyen, V. D., Latva-Ranta, M., & Ruddock, L.
- Affiliations
- University of Oulu (FI)
- Corresponding author
- Ruddock, Lloyd
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2007-12-17
- Volume
- 179
- Issue
- 6
- Pages
- 1193-1204
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2140024
- OpenAlex
- W2112288894
- Cited by
- 256
- References
- 31
- Citations by year
- 2026: 7 · 2025: 14 · 2024: 18 · 2023: 13 · 2022: 16 · 2021: 13 · 2020: 19 · 2019: 12 · 2018: 18 · 2017: 14 · 2016: 14 · 2015: 16 · 2014: 15 · 2013: 12 · 2012: 11
- FWCI
- 3.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- KDEL receptor, ER-associated degradation, Golgi apparatus
- MeSH terms
- Animals, Chlorocebus aethiops, Cloning, Molecular, Endoplasmic Reticulum, Golgi Apparatus, HeLa Cells, Humans, Molecular Sequence Data, Sequence Alignment, Genes, Reporter, Receptors, Peptide, COS Cells, Amino Acid Motifs, Protein Sorting Signals
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