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Published on: December 14, 2015
Identifying novel members of the Wntless interactome through genetic and candidate gene approaches
Jessica Petko1, Trevor Tranchina1, Goral Patel1
1Biology Department, Penn State York, York, PA, United States.
Abstract:
Wnt signaling is an important pathway that regulates several aspects of embryogenesis, stem cell maintenance, and neural connectivity. We have recently determined that opioids decrease Wnt secretion, presumably by inhibiting the recycling of the Wnt trafficking protein Wntless (Wls). This effect appears to be mediated by protein-protein interaction between Wls and the mu-opioid receptor (MOR), the primary cellular target of opioid drugs. The goal of this study was to identify novel protein interactors of Wls that are expressed in the brain and may also play a role in reward or addiction. Using genetic and candidate gene approaches, we show that among a variety of protein, Wls interacts with the dopamine transporter (target of cocaine), cannabinoid receptors (target of THC), Adenosine A2A receptor (target of caffeine), and SGIP1 (endocytic regulator of cannabinoid receptors). Our study shows that aside from opioid receptors, Wntless interacts with additional proteins involved in reward and/or addiction. Future studies will determine whether Wntless and WNT signaling play a more universal role in these processes.
Insights
Opioids reduce Wnt secretion by affecting Wntless protein recycling. This study found Wntless also interacts with proteins linked to addiction, suggesting a broader role in reward pathways.
Area of Science:
- Neuroscience
- Molecular Biology
- Developmental Biology
Background:
- Wnt signaling is crucial for embryonic development, stem cell maintenance, and neural connectivity.
- Opioids are known to decrease Wnt secretion, potentially by interfering with the Wnt trafficking protein Wntless (Wls).
- This opioid-induced effect is thought to involve interactions between Wls and the mu-opioid receptor (MOR).
Purpose of the Study:
- To identify novel brain-expressed protein interactors of Wntless (Wls).
- To explore potential roles of these interactors in reward and addiction pathways.
- To expand understanding beyond opioid receptor interactions with Wls.
Main Methods:
- Utilized genetic approaches to investigate protein interactions.
- Employed candidate gene strategies to screen for Wls interactors.
- Focused on proteins expressed in the brain relevant to reward and addiction.
Main Results:
- Wntless (Wls) was found to interact with several key proteins involved in reward and addiction.
- Identified interactions with the dopamine transporter (a target of cocaine).
- Confirmed interactions with cannabinoid receptors (THC targets), Adenosine A2A receptor (caffeine target), and SGIP1 (an endocytic regulator of cannabinoid receptors).
Conclusions:
- Wntless (Wls) interacts with multiple proteins beyond opioid receptors that are implicated in reward and addiction.
- These findings suggest Wntless and Wnt signaling may have a more widespread role in reward and addiction processes.
- Further research is warranted to elucidate the universal role of Wntless in these complex biological functions.
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