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Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells
Published on: February 21, 2019
The retromer complex influences Wnt secretion by recycling wntless from endosomes to the trans-Golgi network
Tatyana Y Belenkaya1, Yihui Wu, Xiaofang Tang
1Division of Developmental Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45229, USA.
Abstract:
Secreted Wnt proteins play essential roles in many biological processes during development and diseases. However, little is known about the mechanism(s) controlling Wnt secretion. Recent studies have identified Wntless (Wls) and the retromer complex as essential components involved in Wnt signaling. While Wls has been shown to be essential for Wnt secretion, the function(s) of the retromer complex in Wnt signaling is unknown. Here, we have examined a role of Vps35, an essential retromer subunit, in Wnt signaling in Drosophila and mammalian cells. We provide compelling evidence that the retromer complex is required for Wnt secretion. Importantly, Vps35 colocalizes in endosomes and interacts with Wls. Wls becomes unstable in the absence of retromer activity. Our findings link Wls and retromer functions in the same conserved Wnt secretion pathway. We propose that retromer influences Wnt secretion by recycling Wntless from endosomes to the trans-Golgi network (TGN).
Insights
The retromer complex is crucial for Wnt secretion, working with Wntless (Wls). This study reveals retromer recycles Wls, ensuring proper Wnt signaling in development and disease.
Area of Science:
- Cell Biology
- Molecular Biology
- Developmental Biology
Background:
- Secreted Wnt proteins are vital for development and disease.
- Wntless (Wls) and the retromer complex are implicated in Wnt signaling.
- The precise role of the retromer complex in Wnt secretion remains unclear.
Purpose of the Study:
- To investigate the role of Vps35, a retromer subunit, in Wnt signaling.
- To elucidate the functional relationship between the retromer complex and Wntless (Wls) in Wnt secretion.
Main Methods:
- Utilized Drosophila and mammalian cell culture models.
- Examined the colocalization and interaction of Vps35 and Wls.
- Assessed Wnt secretion and Wls stability under varying retromer activity conditions.
Main Results:
- Provided evidence that the retromer complex is essential for Wnt secretion.
- Demonstrated that Vps35 colocalizes with and interacts with Wls in endosomes.
- Showed that Wls stability is compromised in the absence of functional retromer.
Conclusions:
- Established a link between Wntless and retromer functions within the Wnt secretion pathway.
- Proposed a model where retromer facilitates Wnt secretion by recycling Wntless from endosomes to the trans-Golgi network (TGN).
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