| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Institut National de la Santé et de la Recherche Médicale Unité 135 Hormones et Reproduction Hôpital de Bicêtre 94270 Le Kremlin-Bicêtre, France
Scant information is available to date on the intracellular trafficking of the TSH receptor. In the present study we have used stably transfected L cells that express the TSH receptor, 125I-labeled TSH, and antireceptor antibodies as well as gold-conjugated antireceptor monoclonal antibodies and hormone. The latter allowed us to study, by electron microscopy, the cellular distribution and endocytosis of TSH receptor. The receptor was initially localized on the plasmalemma proper and in clathrin-coated pits but was excluded from smooth vesicles open to the cell surface. It was internalized through clathrin-coated vesicles. Constitutive endocytosis represented 10% of cell surface receptor molecules. Endocytosis was increased 3-fold by incubation with hormone. The majority of internalized receptor molecules (90%) was recycled to the cell surface, whereas the hormone was degraded in lysosomes. This recycling of receptor was inhibited by administration of monensin. Electron microscopic and confocal microscopic studies were repeated in primary cultures of human thyroid cells and showed a distribution, and endocytosis pathways, very similar to those observed in transfected L cells. A previous study has shown the LH receptor to be endocytosed in high proportion and to be degraded in lysosomes. Confocal microscopy and colocalization studies with transferrin receptor confirmed that the highly homologous LH and TSH receptors exhibit, when expressed in the same cells, very different cellular trafficking properties. The use of LH/TSH receptor chimeras showed that transmembrane-intracellular domains contain information orienting the protein toward recycling or degradative pathways. The extracellular domain seems to play a role in the extent of internalization. These observations should now allow the identification of the molecular signals involved.
This article has been cited by other articles:
 |
|
 |
|
  S. Tsui, V. Naik, N. Hoa, C. J. Hwang, N. F. Afifiyan, A. Sinha Hikim, A. G. Gianoukakis, R. S. Douglas, and T. J. Smith Evidence for an Association between Thyroid-Stimulating Hormone and Insulin-Like Growth Factor 1 Receptors: A Tale of Two Antigens Implicated in Graves' Disease J. Immunol., September 15, 2008; 181(6): 4397 - 4405. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mohammad, G. Baldini, S. Granell, P. Narducci, A. M. Martelli, and G. Baldini Constitutive Traffic of Melanocortin-4 Receptor in Neuro2A Cells and Immortalized Hypothalamic Neurons J. Biol. Chem., February 16, 2007; 282(7): 4963 - 4974. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Galet and M. Ascoli A Constitutively Active Mutant of the Human Lutropin Receptor (hLHR-L457R) Escapes Lysosomal Targeting and Degradation Mol. Endocrinol., November 1, 2006; 20(11): 2931 - 2945. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Frenzel, C. Voigt, and R. Paschke The Human Thyrotropin Receptor Is Predominantly Internalized by {beta}-Arrestin 2 Endocrinology, June 1, 2006; 147(6): 3114 - 3122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zaitseva, T. Romantseva, J. Manischewitz, J. Wang, D. Goucher, and H. Golding Increased CXCR4-dependent HIV-1 fusion in activated T cells: role of CD4/CXCR4 association J. Leukoc. Biol., December 1, 2005; 78(6): 1306 - 1317. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R S Bhaskaran and M Ascoli The post-endocytotic fate of the gonadotropin receptors is an important determinant of the desensitization of gonadotropin responses J. Mol. Endocrinol., April 1, 2005; 34(2): 447 - 457. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. M. Cox Agonists at {micro}-Opioid Receptors Spin the Wheels to Keep the Action Going Mol. Pharmacol., January 1, 2005; 67(1): 12 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Latif, T. Ando, and T. F. Davies Monomerization as a Prerequisite for Intramolecular Cleavage and Shedding of the Thyrotropin Receptor Endocrinology, December 1, 2004; 145(12): 5580 - 5588. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Xia, S. Kjaer, K. Zheng, P.-S. Hu, L. Bai, J.-Y. Jia, R. Rigler, A. Pramanik, T. Xu, T. Hokfelt, et al. Visualization of a functionally enhanced GFP-tagged galanin R2 receptor in PC12 cells: Constitutive and ligand-induced internalization PNAS, October 19, 2004; 101(42): 15207 - 15212. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Farid and M. W. Szkudlinski Minireview: Structural and Functional Evolution of the Thyrotropin Receptor Endocrinology, September 1, 2004; 145(9): 4048 - 4057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Leterrier, D. Bonnard, D. Carrel, J. Rossier, and Z. Lenkei Constitutive Endocytic Cycle of the CB1 Cannabinoid Receptor J. Biol. Chem., August 20, 2004; 279(34): 36013 - 36021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Beau, M.-T. Groyer-Picard, A. Desroches, E. Condamine, J. Leprince, J.-P. Tome, P. Dessen, H. Vaudry, and M. Misrahi The Basolateral Sorting Signals of the Thyrotropin and Luteinizing Hormone Receptors: An Unusual Family of Signals Sharing an Unusual Distal Intracellular Localization, but Unrelated in Their Structures Mol. Endocrinol., March 1, 2004; 18(3): 733 - 746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
T. Hirakawa, C. Galet, M. Kishi, and M. Ascoli GIPC Binds to the Human Lutropin Receptor (hLHR) through an Unusual PDZ Domain Binding Motif, and It Regulates the Sorting of the Internalized Human Choriogonadotropin and the Density of Cell Surface hLHR J. Biol. Chem., December 5, 2003; 278(49): 49348 - 49357. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Krishnamurthy, H. Kishi, M. Shi, C. Galet, R. S. Bhaskaran, T. Hirakawa, and M. Ascoli Postendocytotic Trafficking of the Follicle-Stimulating Hormone (FSH)-FSH Receptor Complex Mol. Endocrinol., November 1, 2003; 17(11): 2162 - 2176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Qiu, P.-Y. Law, and H. H. Loh {micro}-Opioid Receptor Desensitization: ROLE OF RECEPTOR PHOSPHORYLATION, INTERNALIZATION, AND RESENSITIZATION J. Biol. Chem., September 19, 2003; 278(38): 36733 - 36739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Seck, R. Baron, and W. C. Horne Binding of Filamin to the C-terminal Tail of the Calcitonin Receptor Controls Recycling J. Biol. Chem., March 14, 2003; 278(12): 10408 - 10416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. Chauvin, M. Bencsik, T. Bambino, and R. A. Nissenson Parathyroid Hormone Receptor Recycling: Role of Receptor Dephosphorylation and {beta}-Arrestin Mol. Endocrinol., December 1, 2002; 16(12): 2720 - 2732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Metaye, E. Menet, J. Guilhot, and J.-L. Kraimps Expression and Activity of G Protein-Coupled Receptor Kinases in Differentiated Thyroid Carcinoma J. Clin. Endocrinol. Metab., July 1, 2002; 87(7): 3279 - 3286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ghinea, C. Baratti-Elbaz, A. De Jesus-Lucas, and E. Milgrom TSH Receptor Interaction with the Extracellular Matrix: Role on Constitutive Activity and Sensitivity to Hormonal Stimulation Mol. Endocrinol., May 1, 2002; 16(5): 912 - 923. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
M. Kishi, X. Liu, T. Hirakawa, D. Reczek, A. Bretscher, and M. Ascoli Identification of Two Distinct Structural Motifs That, When Added to the C-Terminal Tail of the Rat LH Receptor, Redirect the Internalized Hormone-Receptor Complex from a Degradation to a Recycling Pathway Mol. Endocrinol., September 1, 2001; 15(9): 1624 - 1635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kishi and M. Ascoli The C-Terminal Tail of the Rat Lutropin/Choriogonadotropin (CG) Receptor Independently Modulates Human (h)CG-Induced Internalization of the Cell Surface Receptor and the Lysosomal Targeting of the Internalized hCG-Receptor Complex Mol. Endocrinol., June 1, 2000; 14(6): 926 - 936. [Abstract] [Full Text]
|
|
|
|
|
|
H. Kishi and M. Ascoli Multiple Distant Amino Acid Residues Present in the Serpentine Region of the Follitropin Receptor Modulate the Rate of Agonist-induced Internalization J. Biol. Chem., September 29, 2000; 275(40): 31030 - 31037. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Parent, P. Labrecque, M. Driss Rochdi, and J. L. Benovic Role of the Differentially Spliced Carboxyl Terminus in Thromboxane A2 Receptor Trafficking. IDENTIFICATION OF A DISTINCT MOTIF FOR TONIC INTERNALIZATION J. Biol. Chem., March 2, 2001; 276(10): 7079 - 7085. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Li, X. Liu, L. Min, and M. Ascoli Mutations of the Second Extracellular Loop of the Human Lutropin Receptor Emphasize the Importance of Receptor Activation and De-emphasize the Importance of Receptor Phosphorylation in Agonist-induced Internalization J. Biol. Chem., March 9, 2001; 276(11): 7968 - 7973. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Latif, P. Graves, and T. F. Davies Oligomerization of the Human Thyrotropin Receptor. FLUORESCENT PROTEIN-TAGGED hTSHR REVEALS POST-TRANSLATIONAL COMPLEXES J. Biol. Chem., November 21, 2001; 276(48): 45217 - 45224. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
