Nephronophthisis: Disease Mechanisms of a Ciliopathy

(A) This cartoon of arenal tubular epithelial cell shows how Wnt signaling occurs primarily through β-catenin–dependent pathways in the absence of urine flow. Ligand binding by the frizzled receptor results in inactivation of the β-catenin destruction complex through the presence of disheveled (Dvl), increased β-catenin levels, and upregulation of effector gene expression of the canonical Wnt signaling pathway. (B) Stimulation of the primary cilium, e.g. by urine flow, results in increased expression of inversin (Inv), which then reduces levels of cytoplasmic Dvl by increasing its proteasomal degradation. This allows reassembly and activation of the β-catenin destruction complex, thereby switching from the canonical to the non-canonical Wnt signaling pathway. The model is consistent with the finding that overexpression of β-catenin (equivalent to canonical Wnt signaling) leads to renal cysts in a mouse model (from: Germino Nature Genet 37:455, 2005).

Publication

Nephronophthisis: Disease Mechanisms of a Ciliopathy. () Friedhelm Hildebrandt, et al. J Am Soc Nephrol. ;20(1):23-35. Figure: F6. Homo sapiens

Disease mentions