The dynein accessory factor Ndel1 stops proliferating cells from regrowing a primary cilium, Inaba et al. reveal.
When quiescent cells reenter the cell cycle, they retract their primary cilium so that the ciliary basal body can be used as a centriole to form one of the two centrosomes that organize the mitotic spindle. A centriolar protein called trichoplein prevents proliferating cells from reassembling a cilium by binding and activating the kinase Aurora A. When cells return to quiescence, the E3 ubiquitin ligase CRL3KCTD17 targets trichoplein for degradation, allowing cilium regeneration.
The dynein accessory factor Ndel1 contains a domain similar to trichoplein and localizes to the mother centriole/basal body. Inaba et al. found that knocking down Ndel1 caused proliferating cells to prematurely degrade trichoplein, resulting in cilium regrowth and cell cycle arrest. This effect was reversed by overexpressing trichoplein or knocking down the ubiquitin ligase subunit KCTD17.
Serum-starved cells transiently down-regulated Ndel1 as they reentered quiescence. Overexpressing Ndel1 prevented these cells from degrading trichoplein and regenerating a cilium. Ndel1 therefore suppresses ciliogenesis and cell cycle exit by stabilizing trichoplein. Accordingly, the kidney epithelia of NDEL1 hypomorphic mice showed an increased number of ciliated, quiescent cells.
Senior author Masaki Inagaki now wants to further explore the relationship between cilia and cell cycle regulation. He points out that, as well as regulating centriole availability, primary cilia act as signaling hubs for numerous growth factors and could therefore have a key role in suppressing tumorigenesis.