QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 9 June 2004
doi: 10.1242/jcs.01168

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.01168v1 117/15/3107    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moore, R. H. Articles by Knoll, B. J. Search for Related Content PubMed PubMed Citation Articles by Moore, R. H. Articles by Knoll, B. J.

Rab11 regulates the recycling and lysosome targeting of ß₂-adrenergic receptors

¹ Department of Pediatrics and Molecular Physiology and Biophysics, Baylor College of Medicine, 6621 Fannin, CCC 1040.00, Houston, TX 77030, USA
² Department of Pharmacological and Pharmaceutical Sciences, University of Houston, 521 Science and Research Building 2, Houston, TX 77204, USA

^* Author for correspondence (e-mail: bknoll{at}uh.edu)

Accepted 19 February 2004

The pericentriolar recycling endosome (RE) may be an alternative compartment through which some ß₂-adrenergic receptors (ß₂ARs) recycle from early endosomes to the cell surface during prolonged exposure to agonist. For the transferrin receptor, CXCR2, and the M₄-muscarinic acetylcholine receptor, trafficking through the RE and receptor recycling is regulated by the small GTPase rab11. The precise role of the RE and rab11 in regulating the cellular trafficking of the ß₂AR is not understood. We therefore monitored trafficking of ß₂ARs in HEK293 cells following the modulation of rab11 activity. Expression of a rab11 mutant deficient in GTP binding (as a fusion between enhanced green fluorescent protein (EGFP) and the rab11S25N mutant) significantly slowed receptor recycling to the cell surface from dispersed transferrin-positive peripheral vesicles following a brief exposure to agonist. The agonist was applied at a time when receptors have undergone only one or two rounds of endocytosis and recycling. In cells overexpressing wild-type rab11, ß₂ARs localized to a rab11-positive compartment and the rate of ß₂AR recycling to the cell surface was reduced, but only after prolonged exposure to agonist and multiple rounds of receptor endocytosis and recycling. This effect was associated with impaired ß₂AR trafficking to lysosomes and receptor proteolysis, whereas the sorting of low-density lipoprotein from transferrin-positive vesicles to late endosomes and lysosomes was not affected. These data highlight a pivotal role for rab11 in regulating the traffic of a G protein-coupled receptor at the level of the RE, where modulation of rab11 activity dictates the balance between receptor recycling and downregulation during prolonged exposure to agonist.

Key words: ß₂-adrenergic receptor, Rab11, Recycling endosome, Lysosome, Trafficking

This article has been cited by other articles:

				J. T. Roland, L. A. Lapierre, and J. R. Goldenring Alternative Splicing in Class V Myosins Determines Association with Rab10 J. Biol. Chem., January 9, 2009; 284(2): 1213 - 1223. [Abstract] [Full Text] [PDF]

				A. D. Zadeh, H. Xu, M. E. Loewen, G. P. Noble, D. F. Steele, and D. Fedida Internalized Kv1.5 traffics via Rab-dependent pathways J. Physiol., October 15, 2008; 586(20): 4793 - 4813. [Abstract] [Full Text] [PDF]

				A. Garcia-Regalado, M. L. Guzman-Hernandez, I. Ramirez-Rangel, E. Robles-Molina, T. Balla, J. Vazquez-Prado, and G. Reyes-Cruz G Protein-coupled Receptor-promoted Trafficking of G{beta}1{gamma}2 Leads to AKT Activation at Endosomes via a Mechanism Mediated by G{beta}1{gamma}2-Rab11a Interaction Mol. Biol. Cell, October 1, 2008; 19(10): 4188 - 4200. [Abstract] [Full Text] [PDF]

				F. Wang, X. Chen, X. Zhang, and L. Ma Phosphorylation State of {micro}-Opioid Receptor Determines the Alternative Recycling of Receptor via Rab4 or Rab11 Pathway Mol. Endocrinol., August 1, 2008; 22(8): 1881 - 1892. [Abstract] [Full Text] [PDF]

				J. T. Roland, A. K. Kenworthy, J. Peranen, S. Caplan, and J. R. Goldenring Myosin Vb Interacts with Rab8a on a Tubular Network Containing EHD1 and EHD3 Mol. Biol. Cell, August 1, 2007; 18(8): 2828 - 2837. [Abstract] [Full Text] [PDF]

				A. P. Reyes-Ibarra, A. Garcia-Regalado, I. Ramirez-Rangel, A. L. Esparza-Silva, M. Valadez-Sanchez, J. Vazquez-Prado, and G. Reyes-Cruz Calcium-Sensing Receptor Endocytosis Links Extracellular Calcium Signaling to Parathyroid Hormone-Related Peptide Secretion via a Rab11a-Dependent and AMSH-Sensitive Mechanism Mol. Endocrinol., June 1, 2007; 21(6): 1394 - 1407. [Abstract] [Full Text] [PDF]

				R. H. Moore, E. E. Millman, V. Godines, N. A. Hanania, T. M. Tran, H. Peng, B. F. Dickey, B. J. Knoll, and R. B. Clark Salmeterol Stimulation Dissociates beta2-Adrenergic Receptor Phosphorylation and Internalization Am. J. Respir. Cell Mol. Biol., February 1, 2007; 36(2): 254 - 261. [Abstract] [Full Text] [PDF]

				D. J. Vaughan, E. E. Millman, V. Godines, J. Friedman, T. M. Tran, W. Dai, B. J. Knoll, R. B. Clark, and R. H. Moore Role of the G Protein-coupled Receptor Kinase Site Serine Cluster in beta2-Adrenergic Receptor Internalization, Desensitization, and beta-Arrestin Translocation J. Biol. Chem., March 17, 2006; 281(11): 7684 - 7692. [Abstract] [Full Text] [PDF]

				M. J. Helms, A. Ambit, P. Appleton, L. Tetley, G. H. Coombs, and J. C. Mottram Bloodstream form Trypanosoma brucei depend upon multiple metacaspases associated with RAB11-positive endosomes J. Cell Sci., March 15, 2006; 119(6): 1105 - 1117. [Abstract] [Full Text] [PDF]

				D. J. Strick and L. A. Elferink Rab15 Effector Protein: A Novel Protein for Receptor Recycling from the Endocytic Recycling Compartment Mol. Biol. Cell, December 1, 2005; 16(12): 5699 - 5709. [Abstract] [Full Text] [PDF]

				A. Swiatecka-Urban, A. Brown, S. Moreau-Marquis, J. Renuka, B. Coutermarsh, R. Barnaby, K. H. Karlson, T. R. Flotte, M. Fukuda, G. M. Langford, et al. The Short Apical Membrane Half-life of Rescued {Delta}F508-Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Results from Accelerated Endocytosis of {Delta}F508-CFTR in Polarized Human Airway Epithelial Cells J. Biol. Chem., November 4, 2005; 280(44): 36762 - 36772. [Abstract] [Full Text] [PDF]

				B. S. Hall, E. Smith, W. Langer, L. A. Jacobs, D. Goulding, and M. C. Field Developmental Variation in Rab11-Dependent Trafficking in Trypanosoma brucei Eukaryot. Cell, May 1, 2005; 4(5): 971 - 980. [Abstract] [Full Text] [PDF]