N-glycosylation of LRP6 by B3GnT2 promotes Wnt/β-Catenin signalling
Reception of Wnt signals by cells is predominantly mediated by Frizzled receptors in conjunction with a co-receptor, the latter being LRP6 or LRP5 for the Wnt/β-catenin signalling pathway. It is important that cells maintain precise control of receptor activation events in order to properly regulate...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
10 March 2023
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| In: |
Cells
Year: 2023, Volume: 12, Issue: 6, Pages: 1-21 |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells12060863 |
| Online Access: | Resolving-System, kostenfrei, Volltext: https://doi.org/10.3390/cells12060863 Verlag, kostenfrei, Volltext: https://www.mdpi.com/2073-4409/12/6/863 
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| Author Notes: | Ruiyao Xu, Xianxian Wang, Sadia Safi, Nico Braunegger, Agnes Hipgrave Ederveen, Michelle Rottmann, Joachim Wittbrodt, Manfred Wuhrer, Janine Wesslowski and Gary Davidson |
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| 520 | |a Reception of Wnt signals by cells is predominantly mediated by Frizzled receptors in conjunction with a co-receptor, the latter being LRP6 or LRP5 for the Wnt/β-catenin signalling pathway. It is important that cells maintain precise control of receptor activation events in order to properly regulate Wnt/β-catenin signalling as aberrant signalling can result in disease in humans. Phosphorylation of the intracellular domain (ICD) of LRP6 is well known to regulate Wntβ-catenin signalling; however, less is known for regulatory post-translational modification events within the extracellular domain (ECD). Using a cell culture-based expression screen for functional regulators of LRP6, we identified a glycosyltransferase, B3GnT2-like, from a teleost fish (medaka) cDNA library, that modifies LRP6 and regulates Wnt/β-catenin signalling. We provide both gain-of-function and loss-of-function evidence that the single human homolog, B3GnT2, promotes extension of polylactosamine chains at multiple N-glycans on LRP6, thereby enhancing trafficking of LRP6 to the plasma membrane and promoting Wnt/β-catenin signalling. Our findings further highlight the importance of LRP6 as a regulatory hub in Wnt signalling and provide one of the few examples of how a specific glycosyltransferase appears to selectively target a signalling pathway component to alter cellular signalling events. | ||
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