Nephronophthisis: Disease Mechanisms of a Ciliopathy

"Cystoproteins” are proteins of genes mutated in cystic kidney diseases of humans, mice, or zebrafish. Depending on cell cycle stage, cystoproteins are localized at different subcellular organelles (shown in grey), including primary cilia, basal bodies, endoplasmic reticulum, the mitotic spindle, centrosomes, adherens junctions or focal adhesions. Arrows in the primary cilium indicate the direction of anterograde transport along the microtubule system mediated by kinesin-2 and retrograde transport by cytoplasmic dynein 1b. A) Most nephrocystins (blue) are located at cilia, the basal body, and centrosome in a cell cycle dependent manner. NPHP1 is also at the transition zone, focal adhesions and adherens junctions. B) Sensory cilia perceive and process cell external signals, and “cystoproteins” are involved in signaling mechanisms downstream of cilial signal recognition. Downstream of cilia (pink), Wnt signaling () and hedgehog signaling () play a role in planar cell polarity, which is mediated (C) partially through orientation of centrosomes and the mitotic spindle poles (). D) Cilia-dependent mechanisms of planar cell polarity seem to be the central to the pathogenesis of the ciliopathies, the most prominent of which are listed on the right. Wht, the Wnti signaling pathway; Shh, the sonic hedgehog signaling pathway.

Publication

Nephronophthisis: Disease Mechanisms of a Ciliopathy. () Friedhelm Hildebrandt, et al. J Am Soc Nephrol. ;20(1):23-35. Figure: F4. All organisms Homo sapiens Danio rerio

Disease mentions