TY - JOUR
T1 - Ultrastructural relationship between the mu opioid receptor and its interacting protein, GPR177, in striatal neurons
AU - Reyes, Arith Ruth S.
AU - Levenson, Robert
AU - Berrettini, Wade
AU - Van Bockstaele, Elisabeth J.
N1 - Funding Information:
This project was supported by the National Institutes of Health grants P20 DA 025995 to W.B. and DA 09082 to E.V.B.
PY - 2010/10/28
Y1 - 2010/10/28
N2 - 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.
AB - 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.
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U2 - 10.1016/j.brainres.2010.08.080
DO - 10.1016/j.brainres.2010.08.080
M3 - Article
C2 - 20813097
AN - SCOPUS:77957372856
SN - 0006-8993
VL - 1358
SP - 71
EP - 80
JO - Brain research
JF - Brain research
ER -