MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Oksche, A.
Right arrow Articles by Rosenthal, W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Oksche, A.
Right arrow Articles by Rosenthal, W.

Vol. 57, Issue 6, 1104-1113, June 2000

Late Endosomal/Lysosomal Targeting and Lack of Recycling of the Ligand-Occupied Endothelin B Receptor

Alexander Oksche, Gregor Boese, Angelika Horstmeyer, Jens Furkert, Michael Beyermann, Michael Bienert, and Walter Rosenthal

Forschungsinstitut für Molekulare Pharmakologie (A.E., G.B., A.H., J.F., M.Be., M.Bi., W.R.) and Institut für Pharmakologie, Freie Universität Berlin (W.R.), Berlin, Germany

A fusion protein consisting of the endothelin B (ETB) receptor and the enhanced green fluorescent protein (EGFP) in conjunction with Cyanin3- or fluorescein-conjugated endothelin 1 (Cy3-ET1, Fluo-ET1) was used to investigate the ligand-mediated internalization of the ETB receptor. The ETB receptor and the ETB/EGFP fusion protein displayed very similar pharmacological properties when expressed in Chinese hamster ovary cells. The integrity of the fusion protein was verified by low temperature PAGE analysis of the 125I-ET1-bound ETB receptor and the 125I-ET1-bound ETB/EGFP fusion protein. Fluorescence microscopy of Chinese hamster ovary cells expressing the ETB/EGFP fusion protein demonstrated strong signals at the plasma membrane. On addition of Cy3-ET1, internalization of ligand and receptor occurred within 5 min via a sucrose-sensitive (i.e., clathrin-mediated) pathway. On further incubation, ETB/EGFP and Cy3-ET1 fluorescences were found in the perinuclear region, colocalized with fluorescent low density lipoproteins, a marker of the late endosomal/lysosomal pathway, but not with fluorescent transferrin, a marker of the recycling pathway. No dissociation of Cy3-ET1 from the receptor was seen within 4 h. Using 125I-ET1 or Cy3-ET1, binding sites were again demonstrable at the cell surface within 2 h. The reappearance of binding sites was abolished by prior treatment of the cells with cycloheximide, an inhibitor of protein synthesis. The data demonstrate that the ligand-occupied ETB receptor is internalized; however, it does not recycle like most of the G protein-coupled receptors but is sorted to the late endosomal/lysosomal pathway in a manner similar to that of the family of protease-activated receptors.

Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Biophys. JHome page
N. J. Evans and J. W. Walker
Endothelin Receptor Dimers Evaluated by FRET, Ligand Binding, and Calcium Mobilization
Biophys. J., July 1, 2008; 95(1): 483 - 492.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M.-T. Bawolak, L. Gera, G. Morissette, J. M. Stewart, and F. Marceau
B-9972 (D-Arg-[Hyp3,Igl5,Oic7,Igl8]-bradykinin) Is an Inactivation-Resistant Agonist of the Bradykinin B2 Receptor Derived from the Peptide Antagonist B-9430 (D-Arg-[Hyp3,Igl5,D-Igl7,Oic8]-bradykinin): Pharmacologic Profile and Effective Induction of Receptor Degradation
J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 534 - 546.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
N. Hatae, N. Aksentijevich, H. W. Zemkova, K. Kretschmannova, M. Tomic, and S. S. Stojilkovic
Cloning and Functional Identification of Novel Endothelin Receptor Type A Isoforms in Pituitary
Mol. Endocrinol., May 1, 2007; 21(5): 1192 - 1204.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
X. Dai and J. J. Galligan
Differential Trafficking and Desensitization of Human ETA and ETB Receptors Expressed in HEK 293 Cells.
Experimental Biology and Medicine, June 1, 2006; 231(6): 746 - 751.
[Abstract] [Full Text] [PDF]

Home page
 Exp. Biol. Med.Home page
E. Grantcharova, H. P. Reusch, M. Beyermann, W. Rosenthal, and A. Oksche
Endothelin A and Endothelin B Receptors Differ in Their Ability to Stimulate ERK1/2 Activation.
Experimental Biology and Medicine, June 1, 2006; 231(6): 757 - 760.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
E. Grantcharova, H. P. Reusch, S. Grossmann, J. Eichhorst, H.-W. Krell, M. Beyermann, W. Rosenthal, and A. Oksche
N-Terminal Proteolysis of the Endothelin B Receptor Abolishes Its Ability to Induce EGF Receptor Transactivation and Contractile Protein Expression in Vascular Smooth Muscle Cells
Arterioscler. Thromb. Vasc. Biol., June 1, 2006; 26(6): 1288 - 1296.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
Z. Kilianova, N. Basora, P. Kilian, M. D. Payet, and N. Gallo-Payet
Human Melanocortin Receptor 2 Expression and Functionality: Effects of Protein Kinase A and Protein Kinase C on Desensitization and Internalization
Endocrinology, May 1, 2006; 147(5): 2325 - 2337.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
G. Giebing, M. Tolle, J. Jurgensen, J. Eichhorst, J. Furkert, M. Beyermann, F. Neuschafer-Rube, W. Rosenthal, W. Zidek, M. van der Giet, et al.
Arrestin-Independent Internalization and Recycling of the Urotensin Receptor Contribute to Long-Lasting Urotensin II-Mediated Vasoconstriction
Circ. Res., September 30, 2005; 97(7): 707 - 715.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
M. J. GERDIN, M. I. MASANA, M. A. RIVERA-BERMUDEZ, R. L. HUDSON, D. J. EARNEST, M. U. GILLETTE, and M. L. DUBOCOVICH
Melatonin desensitizes endogenous MT2 melatonin receptors in the rat suprachiasmatic nucleus: relevance for defining the periods of sensitivity of the mammalian circadian clock to melatonin
FASEB J, November 1, 2004; 18(14): 1646 - 1656.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. Gregan, J. Jurgensen, G. Papsdorf, J. Furkert, M. Schaefer, M. Beyermann, W. Rosenthal, and A. Oksche
Ligand-dependent Differences in the Internalization of Endothelin A and Endothelin B Receptor Heterodimers
J. Biol. Chem., June 25, 2004; 279(26): 27679 - 27687.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
C. Galet, T. Hirakawa, and M. Ascoli
The Postendocytotic Trafficking of the Human Lutropin Receptor Is Mediated by a Transferable Motif Consisting of the C-Terminal Cysteine and an Upstream Leucine
Mol. Endocrinol., February 1, 2004; 18(2): 434 - 446.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. G. Robu, E. S. Pfeiffer, S. L. Robia, R. C. Balijepalli, Y. Pi, T. J. Kamp, and J. W. Walker
Localization of Functional Endothelin Receptor Signaling Complexes in Cardiac Transverse Tubules
J. Biol. Chem., November 28, 2003; 278(48): 48154 - 48161.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. Boivin, D. Chevalier, L. R. Villeneuve, E. Rousseau, and B. G. Allen
Functional Endothelin Receptors Are Present on Nuclei in Cardiac Ventricular Myocytes
J. Biol. Chem., August 1, 2003; 278(31): 29153 - 29163.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
C. Galet, L. Min, R. Narayanan, M. Kishi, N. L. Weigel, and M. Ascoli
Identification of a Transferable Two-Amino-Acid Motif (GT) Present in the C-Terminal Tail of the Human Lutropin Receptor that Redirects Internalized G Protein-Coupled Receptors from a Degradation to a Recycling Pathway
Mol. Endocrinol., March 1, 2003; 17(3): 411 - 422.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Grantcharova, J. Furkert, H. P. Reusch, H.-W. Krell, G. Papsdorf, M. Beyermann, R. Schulein, W. Rosenthal, and A. Oksche
The Extracellular N Terminus of the Endothelin B (ETB) Receptor Is Cleaved by a Metalloprotease in an Agonist-dependent Process
J. Biol. Chem., November 8, 2002; 277(46): 43933 - 43941.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
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]

Home page
 Endocr. Rev.Home page
M. Ascoli, F. Fanelli, and D. L. Segaloff
The Lutropin/Choriogonadotropin Receptor, A 2002 Perspective
Endocr. Rev., April 1, 2002; 23(2): 141 - 174.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
D. R. Bachvarov, S. Houle, M. Bachvarova, J. Bouthillier, A. Adam, and F. Marceau
Bradykinin B2 Receptor Endocytosis, Recycling, and Down-Regulation Assessed Using Green Fluorescent Protein Conjugates
J. Pharmacol. Exp. Ther., April 1, 2001; 297(1): 19 - 26.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
J. D. Paasche, T. Attramadal, C. Sandberg, H. K. Johansen, and H. Attramadal
Mechanisms of Endothelin Receptor Subtype-specific Targeting to Distinct Intracellular Trafficking Pathways
J. Biol. Chem., August 31, 2001; 276(36): 34041 - 34050.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2000 by the American Society for Pharmacology and Experimental Therapeutics