RGD Reference Report - Interaction of the mu-opioid receptor with GPR177 (Wntless) inhibits Wnt secretion: potential implications for opioid dependence. - Rat Genome Database

RGD Reference Report - Interaction of the mu-opioid receptor with GPR177 (Wntless) inhibits Wnt secretion: potential implications for opioid dependence. - Rat Genome Database

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General

Interaction of the mu-opioid receptor with GPR177 (Wntless) inhibits Wnt secretion: potential implications for opioid dependence.
Authors:	Jin, J Kittanakom, S Wong, V Reyes, BA Van Bockstaele, EJ Stagljar, I Berrettini, W Levenson, R
Citation:	Jin J, etal., BMC Neurosci. 2010 Mar 9;11:33. doi: 10.1186/1471-2202-11-33.
RGD ID:	7488961
Pubmed:	PMID:20214800 (View Abstract at PubMed)
PMCID:	PMC2841195 (View Article at PubMed Central)
DOI:	DOI:10.1186/1471-2202-11-33 (Journal Full-text)
BACKGROUND: Opioid agonist drugs produce analgesia. However, long-term exposure to opioid agonists may lead to opioid dependence. The analgesic and addictive properties of opioid agonist drugs are mediated primarily via the mu-opioid receptor (MOR). Opioid agonists appear to alter neuronal morphology in key brain regions implicated in the development of opioid dependence. However, the precise role of the MOR in the development of these neuronal alterations remains elusive. We hypothesize that identifying and characterizing novel MOR interacting proteins (MORIPs) may help to elucidate the underlying mechanisms involved in the development of opioid dependence. RESULTS: GPR177, the mammalian ortholog of Drosophila Wntless/Evi/Sprinter, was identified as a MORIP in a modified split ubiquitin yeast two-hybrid screen. GPR177 is an evolutionarily conserved protein that plays a critical role in mediating Wnt protein secretion from Wnt producing cells. The MOR/GPR177 interaction was validated in pulldown, coimmunoprecipitation, and colocalization studies using mammalian tissue culture cells. The interaction was also observed in rodent brain, where MOR and GPR177 were coexpressed in close spatial proximity within striatal neurons. At the cellular level, morphine treatment caused a shift in the distribution of GPR177 from cytosol to the cell surface, leading to enhanced MOR/GPR177 complex formation at the cell periphery and the inhibition of Wnt protein secretion. CONCLUSIONS: It is known that chronic morphine treatment decreases dendritic arborization and hippocampal neurogenesis, and Wnt proteins are essential for these processes. We therefore propose that the morphine-mediated MOR/GPR177 interaction may result in decreased Wnt secretion in the CNS, resulting in atrophy of dendritic arbors and decreased neurogenesis. Our results demonstrate a previously unrecognized role for GPR177 in regulating cellular response to opioid drugs.

Gene Ontology Annotations Click to see Annotation Detail View

Molecular Function

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
mu-type opioid receptor binding		IPI	Oprm1 (Rattus norvegicus)	7488961		RGD
protein binding	enables	IPI	UniProtKB:Q6P689	7488961	PMID:20214800	IntAct
protein binding	enables	IPI	UniProtKB:P33535	7488961	PMID:20214800	IntAct
protein domain specific binding		IPI	Wls (Rattus norvegicus)	7488961		RGD

Objects Annotated

Genes (Rattus norvegicus)

Oprm1 (opioid receptor, mu 1)

Wls (Wnt ligand secretion mediator)

Additional Information