LRP6

LDL receptor related protein 6

Ensembl:
ENSG00000281324, ENSG00000070018
UniProt:
O75581
OMIM:
603507
Synonyms:
ADCAD2

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

Functional category

  • Ciliary assembly/disassembly
  • Trafficking (BBSome, small GTPases, vesicular transport, ATPases)
  • T cell biology
  • 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 尾-catenin-independent Wnt/Gsk3 sig ling(24837680 , 20059949). Mucociliary Wnt sig ling 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)

Model organism evidence

Mus musculus (3 references)

Compared to wildtype (WT), LZKO CB-MSCs had elongated primary cilia with tapered tips and increased levels of peroxisome proliferator-activated receptor γ (PPARγ), a key transcription factor that favors adipogenesis, and nuclear glucocorticoid receptor (GR), a transcription factor involved in Pp

Primary cilia are WNT-transducing organelles whose biogenesis is controlled by a WNT-PP1 axis.

PMIDs: 39662832, 36693320, 33662399