LRP6

Cilia effects upon perturbation of LRP6

Loss-of-function effect:

Shorter cilia

Ciliogenesis screen results (4 screens)

• Kim2016: Not Reported
• Wheway et al. 2015 (siRNA) [siRNA]: No effect PMID:26167766
• Breslow et al. 2018 (CRISPR) [CRISPR]: No Significant Effect PMID:29459680
• Roosing et al. 2015 (siRNA) [siRNA]: No effect PMID:26595381

Subcellular localization

cilia

References: PMID:36878953, PMID:40892854, PMID:38697898

Functional category

• Ciliary assembly/disassembly
• Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
• Signaling (Hedgehog, GPCRs, ion channels)
• Cardiac & muscle development
• Transcription regulation

Function

Ccnyl1 and its close homolog Cyclin Y (Ccny) activate CDK14/16, which phosphorylate and prime the Wnt co-receptor LRP6 (low-density lipoprotein receptor-related protein 6) for incoming Wnt ligands mostly in β-catenin-independent Wnt/Gsk3 signaling(24837680 , 20059949). Mucociliary Wnt signaling is essential for ciliogenesis and it engages Lrp6 co-receptors that localize to cilia via a VxP ciliary targeting sequence(36878953). Enhancement of Wnt/LRP6 signaling before serum starvation impairs ciliogenesis … reduced Rab8-vesicle docking, failure to remove CP110-CEP97 from mother centrioles … (40892854) Knockdown of ccny/l1 or lrp6 reduces cilium numbers and impairs their morphology. (38697898)