Primary cilia are WNT-transducing organelles whose biogenesis is controlled by a WNT-PP1 axis.
Dev Cell
; 58(2): 139-154.e8, 2023 01 23.
Article
in En
| MEDLINE
| ID: mdl-36693320
ABSTRACT
WNT signaling is important in development, stem cell maintenance, and disease. WNT ligands typically signal via receptor activation across the plasma membrane to induce ß-catenin-dependent gene activation. Here, we show that in mammalian primary cilia, WNT receptors relay a WNT/GSK3 signal that ß-catenin-independently promotes ciliogenesis. Characterization of a LRP6 ciliary targeting sequence and monitoring of acute WNT co-receptor activation (phospho-LRP6) support this conclusion. Ciliary WNT signaling inhibits protein phosphatase 1 (PP1) activity, a negative regulator of ciliogenesis, by preventing GSK3-mediated phosphorylation of the PP1 regulatory inhibitor subunit PPP1R2. Concordantly, deficiency of WNT/GSK3 signaling by depletion of cyclin Y and cyclin-Y-like protein 1 induces primary cilia defects in mouse embryonic neuronal precursors, kidney proximal tubules, and adult mice preadipocytes.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Wnt Proteins
/
Beta Catenin
Limits:
Animals
Language:
En
Journal:
Dev Cell
Journal subject:
EMBRIOLOGIA
Year:
2023
Document type:
Article
Affiliation country: