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The interplay between Wnt and mTOR signaling modulates ciliogenesis in human retinal epithelial cells

The primary cilium is a microtubule-based organelle essential for various cellular functions, particularly signal transduction. While the role of cilia in regulating signaling pathways has been extensively studied, the impact of signaling pathways on cilia formation remains less well understood. Wnt...

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Main Authors: Yuan, Cheng (Author) , Neuner, Annett (Author) , Streubel, Johanna (Author) , Bhanushali, Ayushi (Author) , Simons, Matias (Author) , Acebron, Sergio P. (Author) , Pereira, Gislene (Author)
Format: Article (Journal)
Language:English
Published: September 2, 2025
In: PLoS biology
Year: 2025, Volume: 23, Issue: 9, Pages: 1-22
ISSN:1545-7885
DOI:10.1371/journal.pbio.3003369
Online Access:Resolving-System, kostenfrei, Volltext: https://doi.org/10.1371/journal.pbio.3003369
Verlag, kostenfrei, Volltext: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3003369
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Author Notes:Cheng Yuan, Annett Neuner, Johanna Streubel, Ayushi Bhanushali, Matias Simons, Sergio P. Acebrón, Gislene Pereira
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Summary:The primary cilium is a microtubule-based organelle essential for various cellular functions, particularly signal transduction. While the role of cilia in regulating signaling pathways has been extensively studied, the impact of signaling pathways on cilia formation remains less well understood. Wnt signals are critical modulators of cell fate. In this study, we investigate how modulating Wnt signaling affects cilia formation in human retinal pigment epithelial (hTERT-RPE1) cells. Our findings show that enhancement of Wnt/LRP6 signaling before serum starvation delays ciliogenesis. Cells with high baseline Wnt activity exhibited distal appendage dysregulation, failure to remove CP110-CEP97 from mother centrioles, and reduced Rab8-vesicle docking, which are critical events for cilia membrane establishment and axoneme extension. Additionally, these cells displayed reduced autophagic flux, increased mTOR kinase activity, and elevated OFD1 levels at centriolar satellites. Importantly, mTOR inhibition rescued ciliogenesis in cells with elevated Wnt activity, underscoring the interplay between these signaling pathways. Our data also indicate that insufficient Wnt signaling activation disrupts ciliogenesis, emphasizing the need for precisely regulated Wnt levels.
Item Description:Gesehen am 10.03.2026
Physical Description:Online Resource
ISSN:1545-7885
DOI:10.1371/journal.pbio.3003369

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