![]()
|
|
||||||||
J. Biol. Chem., Vol. 279, Issue 34, 36013-36021, August 20, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||




¶
From the
ESPCI-CNRS UMR 7637, Laboratoire Neurobiologie et Diversité Cellulaire, Ecole Supérieure de Physique et de Chimie Industrielles, 10 Rue Vauquelin, 75231 Paris Cedex 05, France and
INSERM U288, NeuroPsychoPharmacologie Moléculaire, Cellulaire et Fonctionnelle, Faculté de Médecine Pitié-Salpêtrière, 91 bd de l'Hôpital, 75634 Paris Cedex 13, France
The CB1 cannabinoid receptor (CB1R) displays a significant level of ligand-independent (i.e. constitutive) activity, either when heterologously expressed in nonneuronal cells or in neurons where CB1Rs are endogenous. The present study investigates the consequences of constitutive activity on the intracellular trafficking of CB1R. When transfected in HEK-293 cells, CB1R is present at the plasma membrane, but a substantial proportion (
85%) of receptors is localized in intracellular vesicles. Detailed analysis of CB1-EGFP expressed in HEK-293 cells shows that the intracellular CB1R population is mostly of endocytic origin and that treatment with inverse agonist AM281 traps CB1R at the plasma membrane through a monensin-sensitive recycling pathway. Co-transfection with dominant positive or dominant negative mutants of the small GTPases Rab5 and Rab4, but not Rab11, profoundly modifies the steady-state and ligand-induced intracellular distribution of CB1R, indicating that constitutive endocytosis is Rab5-dependent, whereas constitutive recycling is mediated by Rab4. In conclusion, our results indicate that, due to its natural constitutive activity, CB1R permanently and constitutively cycles between plasma membrane and endosomes, leading to a predominantly intracellular localization at steady state.
Received for publication, April 9, 2004 , and in revised form, June 9, 2004.
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s).
* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
The on-line version of this article (available at http://www.jbc.org) contains one movie.
¶ To whom correspondence should be addressed. Tel.: 33-1-40-79-51-84; Fax: 33-1-40-79-47-57; E-mail: zsolt.lenkei{at}espci.fr.
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
![]() |
R. Rozenfeld and L. A. Devi Regulation of CB1 cannabinoid receptor trafficking by the adaptor protein AP-3 FASEB J, July 1, 2008; 22(7): 2311 - 2322. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. Tofighi, B. Joseph, S. Xia, Z.-Q. D. Xu, B. Hamberger, T. Hokfelt, and S. Ceccatelli Galanin decreases proliferation of PC12 cells and induces apoptosis via its subtype 2 receptor (GalR2) PNAS, February 19, 2008; 105(7): 2717 - 2722. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Tappe-Theodor, N. Agarwal, I. Katona, T. Rubino, L. Martini, J. Swiercz, K. Mackie, H. Monyer, D. Parolaro, J. Whistler, et al. A Molecular Basis of Analgesic Tolerance to Cannabinoids J. Neurosci., April 11, 2007; 27(15): 4165 - 4177. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. A. McDonald, C. M. Henstridge, C. N. Connolly, and A. J. Irving An Essential Role for Constitutive Endocytosis, but Not Activity, in the Axonal Targeting of the CB1 Cannabinoid Receptor Mol. Pharmacol., April 1, 2007; 71(4): 976 - 984. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. M. Bohn Constitutive Trafficking--More Than Just Running in Circles? Mol. Pharmacol., April 1, 2007; 71(4): 957 - 958. [Abstract] [Full Text] [PDF] |
||||
![]() |
G. Turu, A. Simon, P. Gyombolai, L. Szidonya, G. Bagdy, Z. Lenkei, and L. Hunyady The Role of Diacylglycerol Lipase in Constitutive and Angiotensin AT1 Receptor-stimulated Cannabinoid CB1 Receptor Activity J. Biol. Chem., March 16, 2007; 282(11): 7753 - 7757. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Martini, M. Waldhoer, M. Pusch, V. Kharazia, J. Fong, J. H. Lee, C. Freissmuth, and J. L. Whistler Ligand-induced down-regulation of the cannabinoid 1 receptor is mediated by the G-protein-coupled receptor-associated sorting protein GASP1 FASEB J, March 1, 2007; 21(3): 802 - 811. [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] |
||||
![]() |
J. Ellis, J. D. Pediani, M. Canals, S. Milasta, and G. Milligan Orexin-1 Receptor-Cannabinoid CB1 Receptor Heterodimerization Results in Both Ligand-dependent and -independent Coordinated Alterations of Receptor Localization and Function J. Biol. Chem., December 15, 2006; 281(50): 38812 - 38824. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. S. Graham, N. Ball, E. L. Scotter, P. Narayan, M. Dragunow, and M. Glass Induction of Krox-24 by Endogenous Cannabinoid Type 1 Receptors in Neuro2A Cells Is Mediated by the MEK-ERK MAPK Pathway and Is Suppressed by the Phosphatidylinositol 3-Kinase Pathway J. Biol. Chem., September 29, 2006; 281(39): 29085 - 29095. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Jacquier, M. Prummer, J.-M. Segura, H. Pick, and H. Vogel Visualizing odorant receptor trafficking in living cells down to the single-molecule level PNAS, September 26, 2006; 103(39): 14325 - 14330. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. W. Paugh, M. P. Cassidy, H. He, S. Milstien, L. J. Sim-Selley, S. Spiegel, and D. E. Selley Sphingosine and Its Analog, the Immunosuppressant 2-Amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol, Interact with the CB1 Cannabinoid Receptor Mol. Pharmacol., July 1, 2006; 70(1): 41 - 50. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Ueda, N. F. Neel, E. Schutyser, D. Raman, and A. Richmond Deletion of the COOH-Terminal Domain of CXC Chemokine Receptor 4 Leads to the Down-regulation of Cell-to-Cell Contact, Enhanced Motility and Proliferation in Breast Carcinoma Cells Cancer Res., June 1, 2006; 66(11): 5665 - 5675. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. M. Filipeanu, F. Zhou, M. L. Lam, K. E. Kerut, W. C. Claycomb, and G. Wu Enhancement of the Recycling and Activation of beta-Adrenergic Receptor by Rab4 GTPase in Cardiac Myocytes J. Biol. Chem., April 21, 2006; 281(16): 11097 - 11103. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. Leterrier, J. Laine, M. Darmon, H. Boudin, J. Rossier, and Z. Lenkei Constitutive activation drives compartment-selective endocytosis and axonal targeting of type 1 cannabinoid receptors. J. Neurosci., March 22, 2006; 26(12): 3141 - 3153. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. D. Holliday, C.-W. Lam, I. R. Tough, and H. M. Cox Role of the C Terminus in Neuropeptide Y Y Receptor Desensitization and Internalization Mol. Pharmacol., March 1, 2005; 67(3): 655 - 664. [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] |
||||
![]() |
B. Holst, N. D. Holliday, A. Bach, C. E. Elling, H. M. Cox, and T. W. Schwartz Common Structural Basis for Constitutive Activity of the Ghrelin Receptor Family J. Biol. Chem., December 17, 2004; 279(51): 53806 - 53817. [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] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |