title: Nerve growth factor-regulated emergence of functional delta-opioid receptors.
abstract: Sorting of intracellular G-protein-coupled receptors (GPCRs) either to lysosomes for degradation or to plasma membrane for surface insertion and functional expression is a key process regulating signaling strength of GPCRs across the plasma membrane in adult mammalian cells. However, little is known about the molecular mechanisms governing the dynamic process of receptor sorting to the plasma membrane for functional expression under normal and pathological conditions. In this study, we demonstrate that delta-opioid receptor (DOPr), a GPCR constitutively targeted to intracellular compartments, is driven to the surface membrane of central synaptic terminals and becomes functional by the neurotrophin nerve growth factor (NGF) in native brainstem neurons. The NGF-triggered DOPr translocation is predominantly mediated by the signaling pathway involving the tyrosine receptor kinase A, Ca(2+)-mobilizing phospholipase C, and Ca(2+)/calmodulin-dependent protein kinase II. Importantly, it requires interactions with the cytoplasmic sorting protein NHERF-1 (Na(+)/H(+) exchange regulatory factor-1) and N-ethyl-maleimide-sensitive factor-regulated exocytosis. In addition, this NGF-mediated mechanism is likely responsible for the emergence of functional DOPr induced by chronic opioids. Thus, NGF may function as a key molecular switch that redirects the sorting of intracellularly targeted DOPr to plasma membrane, resulting in new functional DOPr on central synapses under chronic opioid conditions.
authors.affiliation: Department of Anesthesiology, The University of Texas-MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Bihua
authors.initials: B
authors.lastname: Bie
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.forename: You-Qing
authors.initials: YQ
authors.lastname: Cai
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jaile
authors.initials: J
authors.lastname: Dai
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Lowenstein
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Weinman
authors.forename: Zhizhong Z
authors.initials: ZZ
authors.lastname: Pan
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology; D020932:Nerve Growth Factor / Q000494:pharmacology* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000502:physiology*
chemical_list: D017465:Receptors, Opioid, delta; D009020:Morphine; D020932:Nerve Growth Factor
references.citation: Nat Neurosci. 2001 Apr;4(4):382-90
references.pmid: 11276228
references.citation: Neuron. 1997 Jun;18(6):995-1008
references.pmid: 9208866
references.citation: Annu Rev Neurosci. 2001;24:1217-81
references.pmid: 11520933
references.citation: J Biol Chem. 2000 Apr 14;275(15):11130-40
references.pmid: 10753919
references.citation: Annu Rev Biochem. 2007;76:629-45
references.pmid: 17263661
references.citation: FEBS Lett. 2007 May 22;581(11):2140-9
references.pmid: 17397838
references.citation: Physiol Rev. 2001 Jan;81(1):299-343
references.pmid: 11152760
references.citation: J Biol Chem. 2005 Nov 11;280(45):37974-87
references.pmid: 16144838
references.citation: Prog Neurobiol. 2002 Apr;66(5):285-306
references.pmid: 12015197
references.citation: J Neurosci. 2005 Apr 13;25(15):3824-32
references.pmid: 15829634
references.citation: Science. 2002 Jul 26;297(5581):615-20
references.pmid: 12142540
references.citation: Nat Protoc. 2008;3(11):1718-28
references.pmid: 18927557
references.citation: Life Sci. 2004 Jun 18;75(5):511-36
references.pmid: 15158363
references.citation: Neurochem Res. 2003 Oct;28(10):1443-52
references.pmid: 14570389
references.citation: Trends Pharmacol Sci. 2006 Jun;27(6):324-9
references.pmid: 16678916
references.citation: Annu Rev Cell Dev Biol. 2000;16:19-49
references.pmid: 11031229
references.citation: J Pharmacol Exp Ther. 2009 Apr;329(1):290-6
references.pmid: 19168708
references.citation: Neuron. 2002 Sep 26;36(1):57-68
references.pmid: 12367506
references.citation: Nature. 1992 Nov 26;360(6402):350-2
references.pmid: 1448151
references.citation: Science. 2000 Mar 24;287(5461):2262-7
references.pmid: 10731148
references.citation: EMBO J. 2005 Dec 21;24(24):4211-23
references.pmid: 16319926
references.citation: J Neurosci. 2001 May 1;21(9):3242-50
references.pmid: 11312309
references.citation: Cell. 2009 Jun 12;137(6):1148-59
references.pmid: 19524516
references.citation: Neuron. 2007 Jul 5;55(1):11-24
references.pmid: 17610814
references.citation: Annu Rev Pharmacol Toxicol. 2004;44:559-609
references.pmid: 14744258
references.citation: J Biol Chem. 2004 Dec 24;279(52):54291-303
references.pmid: 15452121
references.citation: Biochem Biophys Res Commun. 2008 Apr 11;368(3):755-60
references.pmid: 18269915
references.citation: J Neurosci. 2003 Mar 15;23(6):2075-85
references.pmid: 12657666
references.citation: Neuron. 2001 Dec 6;32(5):829-39
references.pmid: 11738029
references.citation: Trends Pharmacol Sci. 2007 Jan;28(1):23-31
references.pmid: 17150262
references.citation: J Neurosci. 2005 Mar 23;25(12):3192-8
references.pmid: 15788776
references.citation: Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11470-5
references.pmid: 12169661
references.citation: Annu Rev Physiol. 2006;68:491-505
references.pmid: 16460281
references.citation: J Neurosci Methods. 1980 Dec;3(2):129-49
references.pmid: 6110810
references.citation: Annu Rev Pharmacol Toxicol. 2008;48:537-68
references.pmid: 18184106
references.citation: Trends Pharmacol Sci. 2006 Feb;27(2):85-91
references.pmid: 16376998
references.citation: Annu Rev Biochem. 2003;72:609-42
references.pmid: 12676795
references.citation: Nat Rev Neurosci. 2001 Jan;2(1):24-32
references.pmid: 11253356
references.citation: Nat Rev Neurosci. 2004 Dec;5(12):952-62
references.pmid: 15550950
references.citation: Nature. 1997 Sep 25;389(6649):382-5
references.pmid: 9311779
references.citation: Mol Pharmacol. 2005 Apr;67(4):1137-44
references.pmid: 15608145
references.citation: Cell. 2005 Aug 26;122(4):619-31
references.pmid: 16122428
references.citation: Neuron. 2002 Jan 3;33(1):9-12
references.pmid: 11779474
references.citation: J Neurosci. 2004 Jun 16;24(24):5549-59
references.pmid: 15201327
references.citation: J Neurosci. 2005 Sep 28;25(39):8825-32
references.pmid: 16192372
references.citation: J Biol Chem. 2004 Jun 11;279(24):25002-9
references.pmid: 15070904
references.citation: Pain. 2006 May;122(1-2):163-73
references.pmid: 16527406
references.citation: Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):5135-9
references.pmid: 15044695
references.citation: Mol Pharmacol. 2006 Apr;69(4):1137-45
references.pmid: 16399848