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KDELR1  -  KDEL (Lys-Asp-Glu-Leu) endoplasmic...

Homo sapiens

Synonyms: ER lumen protein-retaining receptor 1, ERD2, ERD2.1, HDEL, KDEL endoplasmic reticulum protein retention receptor 1, ...
 
 
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Disease relevance of KDELR1

 

High impact information on KDELR1

  • Ligand-induced redistribution of a human KDEL receptor from the Golgi complex to the endoplasmic reticulum [4].
  • When either human ERD-2 or a novel human homolog (referred to as ELP-1) is overexpressed in a variety of cell types, the effects are phenotypically indistinguishable from the addition of BFA [5].
  • BFA's ability to alter retrograde traffic from the Golgi to the endoplasmic reticulum (ER) led us to ask whether the ERD-2 retrieval receptor, proposed to return escaped ER resident proteins from the Golgi, might either interfere with or mimic the effects of the drug [5].
  • Sorting of these proteins is dependent on a C-terminal tetrapeptide signal, usually Lys-Asp-Glu-Leu (KDEL in the single letter code) in animal cells, His-Asp-Glu-Leu (HDEL) in Saccharomyces cerevisiae [6].
  • In contrast, Vaux et al. suggest that the mammalian KDEL receptor is a 72K glycoprotein that they detected using an anti-idiotypic antibody approach [6].
 

Chemical compound and disease context of KDELR1

 

Biological context of KDELR1

 

Anatomical context of KDELR1

  • The KDEL receptor is a seven-transmembrane-domain protein that is responsible for the retrieval of endoplasmic reticulum (ER) proteins from the Golgi complex [14].
  • The effect of the expression of the mutant KDEL receptor was consistent with the effect of a specific inhibitor for p38 MAP kinases, because the inhibitor sensitized HeLa cells to ER stress [9].
  • For instance, recycling from the Golgi apparatus back to the ER is sufficient to block the secretion of as much as 90% of an extracellular protein such as the cell wall invertase fused with an HDEL C-terminal tetrapeptide [15].
  • Most likely, this regulation affects retrograde transport from the Golgi complex to the ER, as activated KDEL receptor appears to reside only in retrograde COPI-coated vesicles [16].
  • Fusion proteins comprising a 37-kDa N-glycosylation reporter fused downstream of amino-terminal fragments of the KDEL receptor with varying numbers of hydrophobic regions were synthesized in an in vitro translation system containing canine pancreatic microsomes [17].
 

Associations of KDELR1 with chemical compounds

  • Both thapsigargin, and tunicamycin, increased calreticulin secretion from the cells, although this might be due to more than simply saturation of KDEL receptor binding [10].
  • When the Golgi apparatus is fragmented by nocodazole treatment, a significant portion of rbet1 is not colocalized with structures marked by Golgi mannosidase II or the KDEL receptor [18].
  • Second, treatment with brefeldin A caused gp27 to relocate into peripheral structures positive for both KDEL receptor and COPII [19].
  • It encoded a soluble protein rich in glutamic and aspartic acid with a putative ER retention signal (HDEL) at the C terminus [12].
  • Earlier experiments showing that REDL but not REDLK binds to the KDEL receptor suggested that the terminal lysine is removed sometime during the intoxication process [7].
 

Physical interactions of KDELR1

 

Regulatory relationships of KDELR1

 

Other interactions of KDELR1

  • The KDEL receptor modulates the endoplasmic reticulum stress response through mitogen-activated protein kinase signaling cascades [9].
  • Overexpression of Cdc42 and its activated form Cdc42V12 inhibited the retrograde transport of Shiga toxin from the Golgi complex to the ER, the redistribution of the KDEL receptor, and the ER accumulation of Golgi-resident proteins induced by the active GTP-bound mutant of Sar1 (Sar1[H79G]) [23].
  • The retardation efficiency mediated by this C-terminal peptide segment is comparable with that of the intact LH but lower than that of the KDEL receptor-based retrieval mechanism [24].
  • Overexpression of VIPL redistributed ERGIC-53 to the ER without affecting the cycling of the KDEL-receptor and the overall morphology of the early secretory pathway [25].
  • Blocking its interaction with the KDEL receptor leaves the GAP cytosolic and prevents the deactivation in vivo of Golgi-localized ARF1 [22].
 

Analytical, diagnostic and therapeutic context of KDELR1

References

  1. Anterograde flow of cargo across the golgi stack potentially mediated via bidirectional "percolating" COPI vesicles. Orci, L., Ravazzola, M., Volchuk, A., Engel, T., Gmachl, M., Amherdt, M., Perrelet, A., Sollner, T.H., Rothman, J.E. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  2. The KDEL retrieval system is exploited by Pseudomonas exotoxin A, but not by Shiga-like toxin-1, during retrograde transport from the Golgi complex to the endoplasmic reticulum. Jackson, M.E., Simpson, J.C., Girod, A., Pepperkok, R., Roberts, L.M., Lord, J.M. J. Cell. Sci. (1999) [Pubmed]
  3. Purification and characterization of the human KDEL receptor. Scheel, A.A., Pelham, H.R. Biochemistry (1996) [Pubmed]
  4. Ligand-induced redistribution of a human KDEL receptor from the Golgi complex to the endoplasmic reticulum. Lewis, M.J., Pelham, H.R. Cell (1992) [Pubmed]
  5. A brefeldin A-like phenotype is induced by the overexpression of a human ERD-2-like protein, ELP-1. Hsu, V.W., Shah, N., Klausner, R.D. Cell (1992) [Pubmed]
  6. A human homologue of the yeast HDEL receptor. Lewis, M.J., Pelham, H.R. Nature (1990) [Pubmed]
  7. An early step in Pseudomonas exotoxin action is removal of the terminal lysine residue, which allows binding to the KDEL receptor. Hessler, J.L., Kreitman, R.J. Biochemistry (1997) [Pubmed]
  8. Importance of the glutamate residue of KDEL in increasing the cytotoxicity of Pseudomonas exotoxin derivatives and for increased binding to the KDEL receptor. Kreitman, R.J., Pastan, I. Biochem. J. (1995) [Pubmed]
  9. The KDEL receptor modulates the endoplasmic reticulum stress response through mitogen-activated protein kinase signaling cascades. Yamamoto, K., Hamada, H., Shinkai, H., Kohno, Y., Koseki, H., Aoe, T. J. Biol. Chem. (2003) [Pubmed]
  10. KDEL receptor expression is not coordinatedly up-regulated with ER stress-induced reticuloplasmin expression in HeLa cells. Llewellyn, D.H., Roderick, H.L., Rose, S. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  11. Protein disulfide isomerase and newly synthesized procollagen chains form higher-order structures in the lumen of the endoplasmic reticulum. Kellokumpu, S., Suokas, M., Risteli, L., Myllylä, R. J. Biol. Chem. (1997) [Pubmed]
  12. Endoplasmic reticulum glucosidase II is composed of a catalytic subunit, conserved from yeast to mammals, and a tightly bound noncatalytic HDEL-containing subunit. Trombetta, E.S., Simons, J.F., Helenius, A. J. Biol. Chem. (1996) [Pubmed]
  13. The nuclear envelope serves as an intermediary between the ER and Golgi complex in the intracellular parasite Toxoplasma gondii. Hager, K.M., Striepen, B., Tilney, L.G., Roos, D.S. J. Cell. Sci. (1999) [Pubmed]
  14. Mutational analysis of the human KDEL receptor: distinct structural requirements for Golgi retention, ligand binding and retrograde transport. Townsley, F.M., Wilson, D.W., Pelham, H.R. EMBO J. (1993) [Pubmed]
  15. Protein recycling from the Golgi apparatus to the endoplasmic reticulum in plants and its minor contribution to calreticulin retention. Pagny, S., Cabanes-Macheteau, M., Gillikin, J.W., Leborgne-Castel, N., Lerouge, P., Boston, R.S., Faye, L., Gomord, V. Plant Cell (2000) [Pubmed]
  16. Modulation of intracellular transport by transported proteins: insight from regulation of COPI-mediated transport. Aoe, T., Lee, A.J., van Donselaar, E., Peters, P.J., Hsu, V.W. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  17. Transmembrane topology of the mammalian KDEL receptor. Singh, P., Tang, B.L., Wong, S.H., Hong, W. Mol. Cell. Biol. (1993) [Pubmed]
  18. The mammalian protein (rbet1) homologous to yeast Bet1p is primarily associated with the pre-Golgi intermediate compartment and is involved in vesicular transport from the endoplasmic reticulum to the Golgi apparatus. Zhang, T., Wong, S.H., Tang, B.L., Xu, Y., Peter, F., Subramaniam, V.N., Hong, W. J. Cell Biol. (1997) [Pubmed]
  19. Localization and recycling of gp27 (hp24gamma3): complex formation with other p24 family members. Füllekrug, J., Suganuma, T., Tang, B.L., Hong, W., Storrie, B., Nilsson, T. Mol. Biol. Cell (1999) [Pubmed]
  20. Retention and retrieval: both mechanisms cooperate to maintain calreticulin in the endoplasmic reticulum. Sönnichsen, B., Füllekrug, J., Nguyen Van, P., Diekmann, W., Robinson, D.G., Mieskes, G. J. Cell. Sci. (1994) [Pubmed]
  21. KDEL motif interacts with a specific sequence in mammalian erd2 receptor. Janson, I.M., Toomik, R., O'Farrell, F., Ek, P. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  22. The KDEL receptor regulates a GTPase-activating protein for ADP-ribosylation factor 1 by interacting with its non-catalytic domain. Aoe, T., Huber, I., Vasudevan, C., Watkins, S.C., Romero, G., Cassel, D., Hsu, V.W. J. Biol. Chem. (1999) [Pubmed]
  23. Regulation of protein transport from the Golgi complex to the endoplasmic reticulum by CDC42 and N-WASP. Luna, A., Matas, O.B., Martínez-Menárguez, J.A., Mato, E., Durán, J.M., Ballesta, J., Way, M., Egea, G. Mol. Biol. Cell (2002) [Pubmed]
  24. A single C-terminal peptide segment mediates both membrane association and localization of lysyl hydroxylase in the endoplasmic reticulum. Suokas, M., Myllyla, R., Kellokumpu, S. J. Biol. Chem. (2000) [Pubmed]
  25. Profile-based data base scanning for animal L-type lectins and characterization of VIPL, a novel VIP36-like endoplasmic reticulum protein. Nufer, O., Mitrovic, S., Hauri, H.P. J. Biol. Chem. (2003) [Pubmed]
  26. Evidence for a COP-I-independent transport route from the Golgi complex to the endoplasmic reticulum. Girod, A., Storrie, B., Simpson, J.C., Johannes, L., Goud, B., Roberts, L.M., Lord, J.M., Nilsson, T., Pepperkok, R. Nat. Cell Biol. (1999) [Pubmed]
  27. Identification of amino acids in the binding pocket of the human KDEL receptor. Scheel, A.A., Pelham, H.R. J. Biol. Chem. (1998) [Pubmed]
  28. Endoplasmic reticulum resident proteins of normal human dermal fibroblasts are the major targets for oxidative stress induced by hydrogen peroxide. van der Vlies, D., Pap, E.H., Post, J.A., Celis, J.E., Wirtz, K.W. Biochem. J. (2002) [Pubmed]
  29. Long-lasting aberrant tubulovesicular membrane inclusions accumulate in developing motoneurons after a sublethal excitotoxic insult: a possible model for neuronal pathology in neurodegenerative disease. Tarabal, O., Calderó, J., Lladó, J., Oppenheim, R.W., Esquerda, J.E. J. Neurosci. (2001) [Pubmed]
 
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