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Primary Cilia are WNT Transducing Organelles whose Biogenesis is Regulated by a WNTPP1 axis
Primary Cilia are WNT Transducing Organelles whose Biogenesis is Regulated by a WNTPP1 axis
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Length:
20 minutes
Released:
Dec 10, 2022
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2022.12.09.519813v1?rss=1
Authors: Zhang, K., Da Silva, F., Seidl, C., Wilsch-Bräuninger, M., Herbst, J., Huttner, W. B., Niehrs, C.
Abstract:
WNT signalling is of paramount importance in development, stem cell maintenance, and disease. WNT ligands typically signal via receptor activation at the plasma membrane to induce {beta}-catenin-dependent gene activation. Here we show that in primary cilia, WNT receptors relay a WNT/GSK3 signal that {beta}-catenin-independently promotes ciliogenesis. Innovations supporting this conclusion are monitoring acute WNT co-receptor activation (phospho-LRP6) and identifying and mutating the LRP6 ciliary targeting sequence. Ciliary WNT signalling inhibits protein phosphatase 1 (PP1) activity, a negative regulator of ciliogenesis, by decommissioning GSK3-mediated phosphorylation of the PP1 regulatory inhibitor subunit PPP1R2. Accordingly, deficiency of WNT/GSK3 signalling by depletion of cyclin Y and cyclin-Y-like protein 1 induces widespread primary cilia defects in mouse embryonic neuronal precursors, kidney proximal tubules, and adult mice preadipocytes. We conclude that primary cilia are WNT PP1 signalling organelles.
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Podcast created by Paper Player, LLC
http://biorxiv.org/cgi/content/short/2022.12.09.519813v1?rss=1
Authors: Zhang, K., Da Silva, F., Seidl, C., Wilsch-Bräuninger, M., Herbst, J., Huttner, W. B., Niehrs, C.
Abstract:
WNT signalling is of paramount importance in development, stem cell maintenance, and disease. WNT ligands typically signal via receptor activation at the plasma membrane to induce {beta}-catenin-dependent gene activation. Here we show that in primary cilia, WNT receptors relay a WNT/GSK3 signal that {beta}-catenin-independently promotes ciliogenesis. Innovations supporting this conclusion are monitoring acute WNT co-receptor activation (phospho-LRP6) and identifying and mutating the LRP6 ciliary targeting sequence. Ciliary WNT signalling inhibits protein phosphatase 1 (PP1) activity, a negative regulator of ciliogenesis, by decommissioning GSK3-mediated phosphorylation of the PP1 regulatory inhibitor subunit PPP1R2. Accordingly, deficiency of WNT/GSK3 signalling by depletion of cyclin Y and cyclin-Y-like protein 1 induces widespread primary cilia defects in mouse embryonic neuronal precursors, kidney proximal tubules, and adult mice preadipocytes. We conclude that primary cilia are WNT PP1 signalling organelles.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Dec 10, 2022
Format:
Podcast episode
Titles in the series (100)
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