Regulation of Anterograde Transport of Alpha2-adrenergic Receptors by the N Termini at Multiple Intracellular Compartments

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2006 Oct 14

PMID 17038316

Citations 35

Authors

Chunmin Dong

Guangyu Wu

Affiliations

Soon will be listed here.

Abstract

The studies on the intrinsic structural determinants for export trafficking of G protein-coupled receptors (GPCRs) have been mainly focused on the C termini of the receptors. In this report we determined the role of the extracellular N termini of alpha(2)-adrenergic receptors (alpha(2)-ARs) in the anterograde transport from the endoplasmic reticulum (ER) through the Golgi to the cell surface. The N-terminal-truncated alpha(2B)-AR mutant is completely unable to target to the cell surface. A single Met-6 residue is essential for the export of alpha(2B)-AR from the ER, likely through modulating correct alpha(2B)-AR folding in the ER. The Tyr-Ser motif, highly conserved in the membrane-proximal N termini of all alpha(2)-AR subtypes, is required for the exit of alpha(2A)-AR and alpha(2B)-AR from the Golgi apparatus, thus representing a novel Tyr-based motif modulating GPCR transport at the Golgi level. These data provide the first evidence indicating an essential role of the N termini of GPCRs in the export from distinct intracellular compartments along the secretory pathway.

Citing Articles

Segregation of nascent GPCRs in the ER-to-Golgi transport by CCHCR1 via direct interaction.

Xu X, Qiu L, Zhang M, Wu G J Cell Sci. 2024; 137(3).

PMID: 38230433 PMC: 10912811. DOI: 10.1242/jcs.261685.

Sequence-directed concentration of G protein-coupled receptors in COPII vesicles.

Xu X, Lambert N, Wu G iScience. 2023; 26(10):107969.

PMID: 37810244 PMC: 10551652. DOI: 10.1016/j.isci.2023.107969.

Targeting trafficking as a therapeutic avenue for misfolded GPCRs leading to endocrine diseases.

Ulloa-Aguirre A, Zarinan T, Gutierrez-Sagal R, Tao Y Front Endocrinol (Lausanne). 2022; 13:934685.

PMID: 36093106 PMC: 9452723. DOI: 10.3389/fendo.2022.934685.

Human C1orf27 protein interacts with α-adrenergic receptor and regulates its anterograde transport.

Xu X, Wu G J Biol Chem. 2022; 298(6):102021.

PMID: 35551911 PMC: 9168726. DOI: 10.1016/j.jbc.2022.102021.

Specific motifs mediate post-synaptic and surface transport of G protein-coupled receptors.

Xu X, Wei Z, Wu G iScience. 2022; 25(1):103643.

PMID: 35024582 PMC: 8728401. DOI: 10.1016/j.isci.2021.103643.

References

Stojanovic A, Hwa J . Rhodopsin and retinitis pigmentosa: shedding light on structure and function. Recept Channels. 2002; 8(1):33-50. View

DeGraff J, Gurevich V, Benovic J . The third intracellular loop of alpha 2-adrenergic receptors determines subtype specificity of arrestin interaction. J Biol Chem. 2002; 277(45):43247-52. DOI: 10.1074/jbc.M207495200. View

Grantcharova E, Furkert J, Reusch H, Krell H, Papsdorf G, Beyermann M . The extracellular N terminus of the endothelin B (ETB) receptor is cleaved by a metalloprotease in an agonist-dependent process. J Biol Chem. 2002; 277(46):43933-41. DOI: 10.1074/jbc.M208407200. View

Stockklausner C, Klocker N . Surface expression of inward rectifier potassium channels is controlled by selective Golgi export. J Biol Chem. 2003; 278(19):17000-5. DOI: 10.1074/jbc.M212243200. View

Marchese A, Chen C, Kim Y, Benovic J . The ins and outs of G protein-coupled receptor trafficking. Trends Biochem Sci. 2003; 28(7):369-76. DOI: 10.1016/S0968-0004(03)00134-8. View

Andersson H, DAntona A, Kendall D, von Heijne G, Chin C . Membrane assembly of the cannabinoid receptor 1: impact of a long N-terminal tail. Mol Pharmacol. 2003; 64(3):570-7. DOI: 10.1124/mol.64.3.570. View

Bouley R, Sun T, Chenard M, McLaughlin M, McKee M, Lin H . Functional role of the NPxxY motif in internalization of the type 2 vasopressin receptor in LLC-PK1 cells. Am J Physiol Cell Physiol. 2003; 285(4):C750-62. DOI: 10.1152/ajpcell.00477.2002. View

Wang W, Loh H, Law P . The intracellular trafficking of opioid receptors directed by carboxyl tail and a di-leucine motif in Neuro2A cells. J Biol Chem. 2003; 278(38):36848-58. DOI: 10.1074/jbc.M301540200. View

Bonifacino J, Traub L . Signals for sorting of transmembrane proteins to endosomes and lysosomes. Annu Rev Biochem. 2003; 72:395-447. DOI: 10.1146/annurev.biochem.72.121801.161800. View

10.

Von Zastrow M . Mechanisms regulating membrane trafficking of G protein-coupled receptors in the endocytic pathway. Life Sci. 2003; 74(2-3):217-24. DOI: 10.1016/j.lfs.2003.09.008. View

11.

Wu G, Zhao G, He Y . Distinct pathways for the trafficking of angiotensin II and adrenergic receptors from the endoplasmic reticulum to the cell surface: Rab1-independent transport of a G protein-coupled receptor. J Biol Chem. 2003; 278(47):47062-9. DOI: 10.1074/jbc.M305707200. View

12.

Overton M, Chinault S, Blumer K . Oligomerization, biogenesis, and signaling is promoted by a glycophorin A-like dimerization motif in transmembrane domain 1 of a yeast G protein-coupled receptor. J Biol Chem. 2003; 278(49):49369-77. DOI: 10.1074/jbc.M308654200. View

13.

Tan C, Brady A, Nickols H, Wang Q, Limbird L . Membrane trafficking of G protein-coupled receptors. Annu Rev Pharmacol Toxicol. 2004; 44:559-609. DOI: 10.1146/annurev.pharmtox.44.101802.121558. View

14.

Hague C, Chen Z, Pupo A, Schulte N, Toews M, Minneman K . The N terminus of the human alpha1D-adrenergic receptor prevents cell surface expression. J Pharmacol Exp Ther. 2004; 309(1):388-97. DOI: 10.1124/jpet.103.060509. View

15.

Hague C, Uberti M, Chen Z, Hall R, Minneman K . Cell surface expression of alpha1D-adrenergic receptors is controlled by heterodimerization with alpha1B-adrenergic receptors. J Biol Chem. 2004; 279(15):15541-9. DOI: 10.1074/jbc.M314014200. View

16.

Duvernay M, Zhou F, Wu G . A conserved motif for the transport of G protein-coupled receptors from the endoplasmic reticulum to the cell surface. J Biol Chem. 2004; 279(29):30741-50. DOI: 10.1074/jbc.M313881200. View

17.

Kalatskaya I, Schussler S, Blaukat A, Muller-Esterl W, Jochum M, Proud D . Mutation of tyrosine in the conserved NPXXY sequence leads to constitutive phosphorylation and internalization, but not signaling, of the human B2 bradykinin receptor. J Biol Chem. 2004; 279(30):31268-76. DOI: 10.1074/jbc.M401796200. View

18.

Salahpour A, Angers S, Mercier J, Lagace M, Marullo S, Bouvier M . Homodimerization of the beta2-adrenergic receptor as a prerequisite for cell surface targeting. J Biol Chem. 2004; 279(32):33390-7. DOI: 10.1074/jbc.M403363200. View

19.

Filipeanu C, Zhou F, Claycomb W, Wu G . Regulation of the cell surface expression and function of angiotensin II type 1 receptor by Rab1-mediated endoplasmic reticulum-to-Golgi transport in cardiac myocytes. J Biol Chem. 2004; 279(39):41077-84. DOI: 10.1074/jbc.M405988200. View

20.

Chen W, Goldstein J, Brown M . NPXY, a sequence often found in cytoplasmic tails, is required for coated pit-mediated internalization of the low density lipoprotein receptor. J Biol Chem. 1990; 265(6):3116-23. View