| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on January 7, 2003
Accepted on June 9, 2003
1 Human Reproductive Sciences Unit, Medical Research Council, Edinburgh, United Kingdom.; Divisions of Chemical Pathology and Medical Biochemistry, University of Cape Town Medical School, Cape Town, South Africa.
* To whom correspondence should be addressed. E-mail: r.millar{at}hrsu.mrc.ac.uk.
The chicken gonadotropin-releasing hormone receptor (cGnRH-R) differs from all mammalian GnRH-Rs in possessing a cytoplasmic carboxyl-terminal tail. We have previously demonstrated that the cGnRH-R undergoes more rapid agonist-induced internalization than the mammalian GnRH-Rs, and requires the carboxyl-terminal tail for this process. To investigate the structural determinants mediating this rapid internalization, a series of mutant receptors were generated, including progressive truncations of the tail and substitution of serine and threonine residues with alanine. Truncation of the carboxyl-terminal tail to position 366 and then to position 356, resulted in a progressive attenuation of the rate and total extent of receptor internalization. However, truncation between positions 356 and 346 did not alter the kinetics of internalization further, whereas a further truncation to position 337 resulted in an additional marked reduction of internalization. We show that the membrane proximal Cys328 and the Thr369Thr370-doublet located in the distal carboxyl-terminus play a critical role in mediating rapid internalization. We demonstrate that the cGnRH-R when expressed in both COS-7 and HEK 293 cells, preferentially undergoes rapid agonist-induced internalization in a caveolae-like dynamin-dependent manner, These conclusions are based on our observation that both pretreatments with filipin and methyl-
-cyclodextrin, agents that disrupts lipid-rafts such as caveolae, and coexpression of dominant-negative dynamin-1 (K44A) and caveolin-1 (
1-81) mutants, effectively inhibited rapid agonist-induced internalization. Futhermore, cGnRH-Rs appeared to be mobilized to the -arrestin- and clathrin-coated vesicle-mediated endocytic pathway upon -arrestin overexpression.
This article has been cited by other articles:
 |
|
 |
|
  K. D. G. Pfleger, A. J. Pawson, and R. P. Millar Changes to Gonadotropin-Releasing Hormone (GnRH) Receptor Extracellular Loops Differentially Affect GnRH Analog Binding and Activation: Evidence for Distinct Ligand-Stabilized Receptor Conformations Endocrinology, June 1, 2008; 149(6): 3118 - 3129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Pawson, E. Faccenda, S. Maudsley, Z.-L. Lu, Z. Naor, and R. P. Millar Mammalian Type I Gonadotropin-Releasing Hormone Receptors Undergo Slow, Constitutive, Agonist-Independent Internalization Endocrinology, March 1, 2008; 149(3): 1415 - 1422. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Naor, H. N. Jabbour, M. Naidich, A. J. Pawson, K. Morgan, S. Battersby, M. R. Millar, P. Brown, and R. P. Millar Reciprocal Cross Talk between Gonadotropin-Releasing Hormone (GnRH) and Prostaglandin Receptors Regulates GnRH Receptor Expression and Differential Gonadotropin Secretion Mol. Endocrinol., February 1, 2007; 21(2): 524 - 537. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M R Silver and S A Sower Functional characterization and kinetic studies of an ancestral lamprey GnRH-III selective type II GnRH receptor from the sea lamprey, Petromyzon marinus. J. Mol. Endocrinol., June 1, 2006; 36(3): 601 - 610. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Navratil, T. A. Farmerie, J. Bogerd, T. M. Nett, and C. M. Clay Differential Impact of Intracellular Carboxyl Terminal Domains on Lipid Raft Localization of the Murine Gonadotropin-Releasing Hormone Receptor Biol Reprod, May 1, 2006; 74(5): 788 - 797. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Orlichenko, B. Huang, E. Krueger, and M. A. McNiven Epithelial Growth Factor-induced Phosphorylation of Caveolin 1 at Tyrosine 14 Stimulates Caveolae Formation in Epithelial Cells J. Biol. Chem., February 24, 2006; 281(8): 4570 - 4579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. E. Barran, R. W. Roeske, A. J. Pawson, R. Sellar, M. T. Bowers, K. Morgan, Z.-L. Lu, M. Tsuda, T. Kusakabe, and R. P. Millar Evolution of Constrained Gonadotropin-releasing Hormone Ligand Conformation and Receptor Selectivity J. Biol. Chem., November 18, 2005; 280(46): 38569 - 38575. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N Hislop, C. J Caunt, K. R Sedgley, E. Kelly, S. Mundell, L. D Green, and C. A McArdle Internalization of gonadotropin-releasing hormone receptors (GnRHRs): does arrestin binding to the C-terminal tail target GnRHRs for dynamin-dependent internalization? J. Mol. Endocrinol., August 1, 2005; 35(1): 177 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Pawson, S. Maudsley, K. Morgan, L. Davidson, Z. Naor, and R. P. Millar Inhibition of Human Type I Gonadotropin-Releasing Hormone Receptor (GnRHR) Function by Expression of a Human Type II GnRHR Gene Fragment Endocrinology, June 1, 2005; 146(6): 2639 - 2649. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. K. Cheng and P. C. K. Leung Molecular Biology of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and Their Receptors in Humans Endocr. Rev., April 1, 2005; 26(2): 283 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ronacher, N. Matsiliza, N. Nkwanyana, A. J. Pawson, T. Adam, C. A. Flanagan, R. P. Millar, and A. A. Katz Serine Residues 338 and 339 in the Carboxyl-Terminal Tail of the Type II Gonadotropin-Releasing Hormone Receptor Are Critical for {beta}-Arrestin-Independent Internalization Endocrinology, October 1, 2004; 145(10): 4480 - 4488. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Millar and A. J. Pawson Outside-In and Inside-Out Signaling: The New Concept that Selectivity of Ligand Binding at the Gonadotropin-Releasing Hormone Receptor Is Modulated by the Intracellular Environment Endocrinology, August 1, 2004; 145(8): 3590 - 3593. [Full Text] [PDF]
|
|
|
|
|
|
A. S. Kauffman and E. F. Rissman A Critical Role for the Evolutionarily Conserved Gonadotropin-Releasing Hormone II: Mediation of Energy Status and Female Sexual Behavior Endocrinology, August 1, 2004; 145(8): 3639 - 3646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Estall, B. Yusta, and D. J. Drucker Lipid Raft-dependent Glucagon-like Peptide-2 Receptor Trafficking Occurs Independently of Agonist-induced Desensitization Mol. Biol. Cell, August 1, 2004; 15(8): 3673 - 3687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Millar, Z.-L. Lu, A. J. Pawson, C. A. Flanagan, K. Morgan, and S. R. Maudsley Gonadotropin-Releasing Hormone Receptors Endocr. Rev., April 1, 2004; 25(2): 235 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Kauffman and E. F. Rissman The Evolutionarily Conserved Gonadotropin-Releasing Hormone II Modifies Food Intake Endocrinology, February 1, 2004; 145(2): 686 - 691. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
