![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 54, Issue 3, 525-535, September 1998
Forschungsinstitut für Molekulare Pharmakologie, D-10315
Berlin, Germany (R.S., R.H., A.O., B.W., G.K., W.R.), and
Rudolf-Buchheim-Institut für Pharmakologie, D-35392 Giessen,
Germany (M.D.)
Little is known concerning the intracellular transport of the G
protein-coupled receptors (GPCRs). Previous studies suggested a
functional role for those residues immediately preceding the conserved
palmitoylated cysteine residues in the intracellular carboxyl termini
of some GPCRs in cell surface transport. For the human vasopressin
V2 receptor, we assessed the significance of a dileucine
sequence with an upstream glutamate residue
(ELRSLLCC) in mediating cell surface delivery.
A series of deletion and point mutants in this region were constructed,
and the mutant receptors were expressed in transiently transfected
COS.M6 cells. By using [3H]arginine vasopressin binding
assays to intact cells and immunofluorescence studies with intact and
permeabilized cells, we show that residues E335 (mutant E335Q) and L339
(mutant L339T) are obligatory for receptor transport to the plasma
membrane. Residue L340 has a minor but significant influence.
[3H]Arginine vasopressin binding experiments on membranes
of lysed cells failed to detect any intracellular binding sites for the transport-deficient mutant receptors, suggesting that residues E335 and
L339 participate in receptor folding. Studies with green fluorescent
protein-tagged receptors demonstrate that the bulk of the mutant
receptors E335Q and L339T are trapped in the endoplasmic reticulum.
Complex glycosylation was absent in these mutant receptors, supporting
this conclusion. These data demonstrate that the glutamate/dileucine motif of the vasopressin V2 receptor is critical for the
escape of the receptor from the endoplasmic reticulum, most presumably by establishing a functional and transport-competent folding state. A
databank analysis revealed that these residues are part of a conserved
region in the GPCR family.
This article has been cited by other articles:
|
|
 |
|
  T. Ludwig, S. M. Theissen, M. J. Morton, and M. J. Caplan The Cytoplasmic Tail Dileucine Motif LL572 Determines the Glycosylation Pattern of Membrane-type 1 Matrix Metalloproteinase J. Biol. Chem., December 19, 2008; 283(51): 35410 - 35418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Schwieger, K. Lautz, E. Krause, W. Rosenthal, B. Wiesner, and R. Hermosilla Derlin-1 and p97/Valosin-Containing Protein Mediate the Endoplasmic Reticulum-Associated Degradation of Human V2 Vasopressin Receptors Mol. Pharmacol., March 1, 2008; 73(3): 697 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Urs, A. P. Kowalczyk, and H. Radhakrishna Different Mechanisms Regulate Lysophosphatidic Acid (LPA)-dependent Versus Phorbol Ester-dependent Internalization of the LPA1 Receptor J. Biol. Chem., February 29, 2008; 283(9): 5249 - 5257. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Conn, A. Ulloa-Aguirre, J. Ito, and J. A. Janovick G Protein-Coupled Receptor Trafficking in Health and Disease: Lessons Learned to Prepare for Therapeutic Mutant Rescue in Vivo Pharmacol. Rev., September 1, 2007; 59(3): 225 - 250. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Oueslati, R. Hermosilla, E. Schonenberger, V. Oorschot, M. Beyermann, B. Wiesner, A. Schmidt, J. Klumperman, W. Rosenthal, and R. Schulein Rescue of a Nephrogenic Diabetes Insipidus-causing Vasopressin V2 Receptor Mutant by Cell-penetrating Peptides J. Biol. Chem., July 13, 2007; 282(28): 20676 - 20685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Matsumoto, K. Narzinski, G. V. Nikiforovich, and T. J. Baranski A Comprehensive Structure-Function Map of the Intracellular Surface of the Human C5a Receptor: II. ELUCIDATION OF G PROTEIN SPECIFICITY DETERMINANTS J. Biol. Chem., February 2, 2007; 282(5): 3122 - 3133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Matsumoto, K. Narzinski, P. D. Kiser, G. V. Nikiforovich, and T. J. Baranski A Comprehensive Structure-Function Map of the Intracellular Surface of the Human C5a Receptor: I. IDENTIFICATION OF CRITICAL RESIDUES J. Biol. Chem., February 2, 2007; 282(5): 3105 - 3121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Dong and G. Wu Regulation of Anterograde Transport of {alpha}2-Adrenergic Receptors by the N Termini at Multiple Intracellular Compartments J. Biol. Chem., December 15, 2006; 281(50): 38543 - 38554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Carrel, M. Hamon, and M. Darmon Role of the C-terminal di-leucine motif of 5-HT1A and 5-HT1B serotonin receptors in plasma membrane targeting J. Cell Sci., October 15, 2006; 119(20): 4276 - 4284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Drake, S. K. Shenoy, and R. J. Lefkowitz Trafficking of G Protein-Coupled Receptors Circ. Res., September 15, 2006; 99(6): 570 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Rutz, A. Renner, M. Alken, K. Schulz, M. Beyermann, B. Wiesner, W. Rosenthal, and R. Schulein The Corticotropin-releasing Factor Receptor Type 2a Contains an N-terminal Pseudo Signal Peptide J. Biol. Chem., August 25, 2006; 281(34): 24910 - 24921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kuwasako, Y.-N. Cao, C.-P. Chu, S. Iwatsubo, T. Eto, and K. Kitamura Functions of the Cytoplasmic Tails of the Human Receptor Activity-modifying Protein Components of Calcitonin Gene-related Peptide and Adrenomedullin Receptors J. Biol. Chem., March 17, 2006; 281(11): 7205 - 7213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Seck, M. Pellegrini, A. M. Florea, V. Grignoux, R. Baron, D. F. Mierke, and W. C. Horne The {Delta}e13 Isoform of the Calcitonin Receptor Forms a Six-Transmembrane Domain Receptor with Dominant-Negative Effects on Receptor Surface Expression and Signaling Mol. Endocrinol., August 1, 2005; 19(8): 2132 - 2144. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Robben, N. V. A. M. Knoers, and P. M. T. Deen Characterization of vasopressin V2 receptor mutants in nephrogenic diabetes insipidus in a polarized cell model Am J Physiol Renal Physiol, August 1, 2005; 289(2): F265 - F272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Robert, E. Clauser, P. X. Petit, and M. A. Ventura A Novel C-terminal Motif Is Necessary for the Export of the Vasopressin V1b/V3 Receptor to the Plasma Membrane J. Biol. Chem., January 21, 2005; 280(3): 2300 - 2308. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.H. Robben, N.V.A.M. Knoers, and P.M.T. Deen Regulation of the Vasopressin V2 Receptor by Vasopressin in Polarized Renal Collecting Duct Cells Mol. Biol. Cell, December 1, 2004; 15(12): 5693 - 5699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Nickols, V. N. Shah, W. J. Chazin, and L. E. Limbird Calmodulin Interacts with the V2 Vasopressin Receptor: ELIMINATION OF BINDING TO THE C TERMINUS ALSO ELIMINATES ARGININE VASOPRESSIN-STIMULATED ELEVATION OF INTRACELLULAR CALCIUM J. Biol. Chem., November 5, 2004; 279(45): 46969 - 46980. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Duvernay, F. Zhou, and G. Wu A Conserved Motif for the Transport of G Protein-coupled Receptors from the Endoplasmic Reticulum to the Cell Surface J. Biol. Chem., July 16, 2004; 279(29): 30741 - 30750. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Gaudreau, M.-E. Beaulieu, Z. Chen, C. Le Gouill, P. Lavigne, J. Stankova, and M. Rola-Pleszczynski Structural Determinants Regulating Expression of the High Affinity Leukotriene B4 Receptor: INVOLVEMENT OF DILEUCINE MOTIFS AND {alpha}-HELIX VIII J. Biol. Chem., March 12, 2004; 279(11): 10338 - 10345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Okuno, H. Ago, K. Terawaki, M. Miyano, T. Shimizu, and T. Yokomizo Helix 8 of the Leukotriene B4 Receptor Is Required for the Conformational Change to the Low Affinity State after G-protein Activation J. Biol. Chem., October 17, 2003; 278(42): 41500 - 41509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wang, H. H. Loh, and P.-Y. Law The Intracellular Trafficking of Opioid Receptors Directed by Carboxyl Tail and a Di-leucine Motif in Neuro2A Cells J. Biol. Chem., September 19, 2003; 278(38): 36848 - 36858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Tan, H. H. Nickols, and L. E. Limbird Appropriate Polarization following Pharmacological Rescue of V2 Vasopressin Receptors Encoded by X-linked Nephrogenic Diabetes Insipidus Alleles Involves a Conformation of the Receptor That Also Attains Mature Glycosylation J. Biol. Chem., September 12, 2003; 278(37): 35678 - 35686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Chaipatikul, L. J. Erickson-Herbrandson, H. H. Loh, and P.-Y. Law Rescuing the Traffic-Deficient Mutants of Rat {micro}-Opioid Receptors with Hydrophobic Ligands Mol. Pharmacol., July 1, 2003; 64(1): 32 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. VanLeeuwen, M. E. Steffey, C. Donahue, G. Ho, and R. G. MacKenzie Cell Surface Expression of the Melanocortin-4 Receptor Is Dependent on a C-terminal Di-isoleucine Sequence at Codons 316/317 J. Biol. Chem., April 25, 2003; 278(18): 15935 - 15940. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kochl, M. Alken, C. Rutz, G. Krause, A. Oksche, W. Rosenthal, and R. Schulein The Signal Peptide of the G Protein-coupled Human Endothelin B Receptor Is Necessary for Translocation of the N-terminal Tail across the Endoplasmic Reticulum Membrane J. Biol. Chem., May 3, 2002; 277(18): 16131 - 16138. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Syed, N. J. Beaumont, A. Patel, C. E. Naylor, H. K. Bayele, C. L. Joannou, P. S.N. Rowe, R. W. Evans, and S. K. S. Srai Analysis of the human hephaestin gene and protein: comparative modelling of the N-terminus ecto-domain based upon ceruloplasmin Protein Eng. Des. Sel., March 1, 2002; 15(3): 205 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Bermak and Q.-Y. Zhou Accessory Proteins in the Biogenesis of G Protein-Coupled Receptors Mol. Interv., December 1, 2001; 1(5): 282 - 287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Gu, X. Wu, B. Giros, M. G. Caron, M. J. Caplan, and G. Rudnick The NH2-terminus of Norepinephrine Transporter Contains a Basolateral Localization Signal for Epithelial Cells Mol. Biol. Cell, December 1, 2001; 12(12): 3797 - 3807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Hermosilla and R. Schulein Sorting Functions of the Individual Cytoplasmic Domains of the G Protein-Coupled Vasopressin V2 Receptor in Madin Darby Canine Kidney Epithelial Cells Mol. Pharmacol., November 1, 2001; 60(5): 1031 - 1039. [Abstract] [Full Text]
|
|
|
|
|
|
S. Venkatesan, A. Petrovic, M. Locati, Y.-O. Kim, D. Weissman, and P. M. Murphy A Membrane-proximal Basic Domain and Cysteine Cluster in the C-terminal Tail of CCR5 Constitute a Bipartite Motif Critical for Cell Surface Expression J. Biol. Chem., October 19, 2001; 276(43): 40133 - 40145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kristiansen, W. K. Kroeze, D. L. Willins, E. I. Gelber, J. E. Savage, R. A. Glennon, and B. L. Roth A Highly Conserved Aspartic Acid (Asp-155) Anchors the Terminal Amine Moiety of Tryptamines and Is Involved in Membrane Targeting of the 5-HT2A Serotonin Receptor But Does Not Participate in Activation via a "Salt-Bridge Disruption" Mechanism J. Pharmacol. Exp. Ther., June 1, 2000; 293(3): 735 - 746. [Abstract] [Full Text]
|
|
|
|
|
|
J. Wang, L. Wang, J. Zheng, J. L. Anderson, and M. L. Toews Identification of Distinct Carboxyl-Terminal Domains Mediating Internalization and Down-Regulation of the Hamster alpha 1B- Adrenergic Receptor Mol. Pharmacol., April 1, 2000; 57(4): 687 - 694. [Abstract] [Full Text]
|
|
|
|
|
|
G. Krause, R. Hermosilla, A. Oksche, C. Rutz, W. Rosenthal, and R. Schülein Molecular and Conformational Features of a Transport-Relevant Domain in the C-Terminal Tail of the Vasopressin V2 Receptor Mol. Pharmacol., February 1, 2000; 57(2): 232 - 242. [Abstract] [Full Text]
|
|
|
|
|
|
G. Ho and R. G. MacKenzie Functional Characterization of Mutations in Melanocortin-4 Receptor Associated with Human Obesity J. Biol. Chem., December 10, 1999; 274(50): 35816 - 35822. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Nakamura and M. Ascoli A Dileucine-Based Motif in the C-Terminal Tail of the Lutropin/Choriogonadotropin Receptor Inhibits Endocytosis of the Agonist-Receptor Complex Mol. Pharmacol., October 1, 1999; 56(4): 728 - 736. [Abstract] [Full Text]
|
|
|
|
|
|
Z. Xu, A. Hirasawa, H. Shinoura, and G. Tsujimoto Interaction of the alpha 1B-Adrenergic Receptor with gC1q-R, a Multifunctional Protein J. Biol. Chem., July 23, 1999; 274(30): 21149 - 21154. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sharma, A. Crane, J. P. Clement IV, G. Gonzalez, A. P. Babenko, J. Bryan, and L. Aguilar-Bryan The C Terminus of SUR1 Is Required for Trafficking of KATP Channels J. Biol. Chem., July 16, 1999; 274(29): 20628 - 20632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Berrada, C. L. Plesnicher, X. Luo, and M. Thibonnier Dynamic Interaction of Human Vasopressin/Oxytocin Receptor Subtypes with G Protein-coupled Receptor Kinases and Protein Kinase C after Agonist Stimulation J. Biol. Chem., August 25, 2000; 275(35): 27229 - 27237. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. N. Manganas and J. S. Trimmer Subunit Composition Determines Kv1 Potassium Channel Surface Expression J. Biol. Chem., September 15, 2000; 275(38): 29685 - 29693. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. V. Sandoval, S. Martinez-Arca, J. Valdueza, S. Palacios, and G. D. Holman Distinct Reading of Different Structural Determinants Modulates the Dileucine-mediated Transport Steps of the Lysosomal Membrane Protein LIMPII and the Insulin-sensitive Glucose Transporter GLUT4 J. Biol. Chem., December 15, 2000; 275(51): 39874 - 39885. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Schulein, K. Zuhlke, G. Krause, and W. Rosenthal Functional Rescue of the Nephrogenic Diabetes Insipidus-causing Vasopressin V2 Receptor Mutants G185C and R202C by a Second Site Suppressor Mutation J. Biol. Chem., March 9, 2001; 276(11): 8384 - 8392. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
