title: Ultrastructural relationship between the mu opioid receptor and its interacting protein, GPR177, in striatal neurons.
abstract: GPR177, the mammalian ortholog of Drosophila Wntless/Evi/Sprinter, was recently identified as a novel mu-opioid receptor (MOR) interacting protein. GPR177 is a trans-membrane protein pivotal to mediating the secretion of Wnt signaling proteins. Wnt proteins, in turn, are essential in regulating neuronal development, a phenomenon inhibited upon chronic exposure to MOR agonists such as morphine and heroin. We previously showed that GPR177 and MOR are co-localized in the mouse dorsolateral striatum; however, the nature of this interaction was not fully elucidated. Therefore, in the present study, we examined cellular substrates for interactions between GPR177 and MOR using a combined immunogold-silver and peroxidase detection approach in coronal sections in the dorsolateral segment of the striatum. Semi-quantitative analysis of the ultrastructural distribution of GPR177 and MOR in striatal somata and in dendritic processes showed that, of the somata and dendritic processes exhibiting GPR177, 32% contained MOR immunolabeling while for profiles exhibiting MOR, 37% also contained GPR177 immunoreactivity. GPR177-labeled particles were localized predominantly along both the plasma membrane and within the cytoplasm of MOR-labeled dendrites. Somata and dendritic processes that contained both GPR177 and MOR more often received symmetric (inhibitory-type) synapses from unlabeled axon terminals. To further define the phenotype of GPR177 and MOR-containing cellular profiles, triple immunofluorescence detection showed that GPR177 and MOR are localized in neurons containing the opioid peptide, enkephalin, within the dorsolateral striatum. The results provide an anatomical substrate for interactions between MOR and its interacting protein, GPR177, in striatal opioid-containing neurons that may underlie the morphological alterations produced in neurons by chronic opiate use.
authors.affiliation: Department of Neuroscience, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Arith-Ruth S
authors.initials: AR
authors.lastname: Reyes
authors.forename: Robert
authors.initials: R
authors.lastname: Levenson
authors.forename: Wade
authors.initials: W
authors.lastname: Berrettini
authors.forename: Elisabeth J
authors.initials: EJ
authors.lastname: Van Bockstaele
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000166:cytology; D004745:Enkephalins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016253:Microscopy, Immunoelectron / Q000379:methods; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism* / Q000648:ultrastructure*; D017450:Receptors, Opioid, mu / Q000378:metabolism* / Q000648:ultrastructure*; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D004745:Enkephalins; C545200:Gpr177 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D017450:Receptors, Opioid, mu
references.citation: Trends Neurosci. 1989 Oct;12(10):366-75
references.pmid: 2479133
references.citation: J Biol Chem. 1994 Aug 12;269(32):20548-53
references.pmid: 8051154
references.citation: Cell. 2006 May 5;125(3):523-33
references.pmid: 16678096
references.citation: Curr Opin Neurobiol. 2004 Jun;14(3):370-8
references.pmid: 15194118
references.citation: Nat Rev Neurosci. 2005 May;6(5):351-62
references.pmid: 15832199
references.citation: J Neurosci Methods. 1980 Dec;3(2):129-49
references.pmid: 6110810
references.citation: J Neurochem. 1977 Aug;29(2):221-30
references.pmid: 301925
references.citation: Curr Opin Neurobiol. 2010 Apr;20(2):199-204
references.pmid: 20167474
references.citation: Neuroscience. 1999;88(3):795-810
references.pmid: 10363818
references.citation: J Anat. 1959 Oct;93:420-33
references.pmid: 13829103
references.citation: Brain Res. 1996 Aug 26;731(1-2):141-54
references.pmid: 8883864
references.citation: J Comp Neurol. 1996 Nov 25;375(4):659-74
references.pmid: 8930791
references.citation: Annu Rev Neurosci. 1986;9:357-81
references.pmid: 3085570
references.citation: Curr Opin Pharmacol. 2005 Feb;5(1):60-8
references.pmid: 15661627
references.citation: Annu Rev Neurosci. 2008;31:339-58
references.pmid: 18558859
references.citation: J Comp Neurol. 1999 Sep 13;412(1):132-46
references.pmid: 10440715
references.citation: Synapse. 1999 Aug;33(2):160-2
references.pmid: 10400894
references.citation: Annu Rev Biochem. 2004;73:953-90
references.pmid: 15189164
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18598-603
references.pmid: 19841259
references.citation: J Neurosci Res. 1992 Feb;31(2):212-30
references.pmid: 1349353
references.citation: Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7579-84
references.pmid: 10840056
references.citation: Development. 2006 Dec;133(24):4901-11
references.pmid: 17108000
references.citation: Brain Res. 1994 Apr 18;643(1-2):245-65
references.pmid: 8032920
references.citation: J Comp Neurol. 1985 Feb 22;232(4):481-98
references.pmid: 2579980
references.citation: Learn Mem. 2009 Aug 27;16(9):564-72
references.pmid: 19713355
references.citation: Curr Opin Neurobiol. 2003 Jun;13(3):348-53
references.pmid: 12850220
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11202-7
references.pmid: 8855333
references.citation: J Comp Neurol. 1994 Dec 15;350(3):412-38
references.pmid: 7884049
references.citation: AAPS J. 2005 Oct 19;7(3):E587-91
references.pmid: 16353937
references.citation: Mol Pain. 2008 Sep 30;4:41
references.pmid: 18826595
references.citation: Neuromolecular Med. 2005;7(1-2):51-9
references.pmid: 16052038
references.citation: Synapse. 2003 Mar 15;47(4):255-61
references.pmid: 12539198
references.citation: Trends Neurosci. 1996 Jan;19(1):19-24
references.pmid: 8787136
references.citation: Nat Cell Biol. 2008 Feb;10(2):170-7
references.pmid: 18193037
references.citation: Neurobiol Learn Mem. 1998 Jul-Sep;70(1-2):119-36
references.pmid: 9753592
references.citation: Drugs. 2004;64(23):2629-38
references.pmid: 15537367
references.citation: Cell. 2006 May 5;125(3):509-22
references.pmid: 16678095
references.citation: Annu Rev Neurosci. 2008;31:359-87
references.pmid: 18558860
references.citation: Brain Res. 1985 Feb 18;327(1-2):307-11
references.pmid: 3986508
references.citation: BMC Neurosci. 2010 Mar 09;11:33
references.pmid: 20214800
references.citation: Trends Pharmacol Sci. 1999 Jan;20(1):19-26
references.pmid: 10101958
references.citation: J Neurosci. 2004 Sep 8;24(36):7916-22
references.pmid: 15356204
references.citation: Trends Neurosci. 1990 Jul;13(7):244-54
references.pmid: 1695398
references.citation: J Biol Chem. 2001 Aug 17;276(33):31408-14
references.pmid: 11359768
references.citation: Mol Pharmacol. 2005 Jan;67(1):280-7
references.pmid: 15475572
references.citation: J Neurosci. 1996 Aug 15;16(16):5037-48
references.pmid: 8756434
references.citation: Neuroscience. 2007 Jan 5;144(1):77-87
references.pmid: 17055658
references.citation: J Comp Neurol. 1996 Dec 02;376(1):65-74
references.pmid: 8946284
references.citation: Brain Res. 2007 Jun 4;1152:49-56
references.pmid: 17459351
references.citation: Eur J Neurosci. 2005 Jan;21(2):493-500
references.pmid: 15673448