Nerve growth factor-regulated emergence of functional delta-opioid receptors.
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.
Bie
Bihua
B
Department of Anesthesiology, The University of Texas-MD Anderson Cancer Center, Houston, Texas 77030, USA.
Zhang
Zhi
Z
Cai
You-Qing
YQ
Zhu
Wei
W
Zhang
Yong
Y
Dai
Jaile
J
Lowenstein
Charles J
CJ
Weinman
Edward J
EJ
Pan
Zhizhong Z
ZZ
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*
D017465:Receptors, Opioid, delta; D009020:Morphine; D020932:Nerve Growth Factor
Nat Neurosci. 2001 Apr;4(4):382-90
11276228
Neuron. 1997 Jun;18(6):995-1008
9208866
Annu Rev Neurosci. 2001;24:1217-81
11520933
J Biol Chem. 2000 Apr 14;275(15):11130-40
10753919
Annu Rev Biochem. 2007;76:629-45
17263661
FEBS Lett. 2007 May 22;581(11):2140-9
17397838
Physiol Rev. 2001 Jan;81(1):299-343
11152760
J Biol Chem. 2005 Nov 11;280(45):37974-87
16144838
Prog Neurobiol. 2002 Apr;66(5):285-306
12015197
J Neurosci. 2005 Apr 13;25(15):3824-32
15829634
Science. 2002 Jul 26;297(5581):615-20
12142540
Nat Protoc. 2008;3(11):1718-28
18927557
Life Sci. 2004 Jun 18;75(5):511-36
15158363
Neurochem Res. 2003 Oct;28(10):1443-52
14570389
Trends Pharmacol Sci. 2006 Jun;27(6):324-9
16678916
Annu Rev Cell Dev Biol. 2000;16:19-49
11031229
J Pharmacol Exp Ther. 2009 Apr;329(1):290-6
19168708
Neuron. 2002 Sep 26;36(1):57-68
12367506
Nature. 1992 Nov 26;360(6402):350-2
1448151
Science. 2000 Mar 24;287(5461):2262-7
10731148
EMBO J. 2005 Dec 21;24(24):4211-23
16319926
J Neurosci. 2001 May 1;21(9):3242-50
11312309
Cell. 2009 Jun 12;137(6):1148-59
19524516
Neuron. 2007 Jul 5;55(1):11-24
17610814
Annu Rev Pharmacol Toxicol. 2004;44:559-609
14744258
J Biol Chem. 2004 Dec 24;279(52):54291-303
15452121
Biochem Biophys Res Commun. 2008 Apr 11;368(3):755-60
18269915
J Neurosci. 2003 Mar 15;23(6):2075-85
12657666
Neuron. 2001 Dec 6;32(5):829-39
11738029
Trends Pharmacol Sci. 2007 Jan;28(1):23-31
17150262
J Neurosci. 2005 Mar 23;25(12):3192-8
15788776
Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11470-5
12169661
Annu Rev Physiol. 2006;68:491-505
16460281
J Neurosci Methods. 1980 Dec;3(2):129-49
6110810
Annu Rev Pharmacol Toxicol. 2008;48:537-68
18184106
Trends Pharmacol Sci. 2006 Feb;27(2):85-91
16376998
Annu Rev Biochem. 2003;72:609-42
12676795
Nat Rev Neurosci. 2001 Jan;2(1):24-32
11253356
Nat Rev Neurosci. 2004 Dec;5(12):952-62
15550950
Nature. 1997 Sep 25;389(6649):382-5
9311779
Mol Pharmacol. 2005 Apr;67(4):1137-44
15608145
Cell. 2005 Aug 26;122(4):619-31
16122428
Neuron. 2002 Jan 3;33(1):9-12
11779474
J Neurosci. 2004 Jun 16;24(24):5549-59
15201327
J Neurosci. 2005 Sep 28;25(39):8825-32
16192372
J Biol Chem. 2004 Jun 11;279(24):25002-9
15070904
Pain. 2006 May;122(1-2):163-73
16527406
Proc Natl Acad Sci U S A. 2004 Apr 6;101(14):5135-9
15044695
Mol Pharmacol. 2006 Apr;69(4):1137-45
16399848