Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein-Aurora A pathway.

The Journal of cell biology 2016 Feb 15

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Primary cilia protrude from the surface of quiescent cells and disassemble at cell cycle reentry. We previously showed that ciliary reassembly is suppressed by trichoplein-mediated Aurora A activation pathway in growing cells. Here, we report that Ndel1, a well-known modulator of dynein activity, localizes at the subdistal appendage of the mother centriole, which nucleates a primary cilium. In the presence of serum, Ndel1 depletion reduces trichoplein at the mother centriole and induces unscheduled primary cilia formation, which is reverted by forced trichoplein expression or coknockdown of KCTD17 (an E3 ligase component protein for trichoplein). Serum starvation induced transient Ndel1 degradation, subsequent to the disappearance of trichoplein at the mother centriole. Forced expression of Ndel1 suppressed trichoplein degradation and axonemal microtubule extension during ciliogenesis, similar to trichoplein induction or KCTD17 knockdown. Most importantly, the proportion of ciliated and quiescent cells was increased in the kidney tubular epithelia of newborn Ndel1-hypomorphic mice. Thus, Ndel1 acts as a novel upstream regulator of the trichoplein-Aurora A pathway to inhibit primary cilia assembly. © 2016 Inaba et al.

Citation

Hironori Inaba, Hidemasa Goto, Kousuke Kasahara, Kanako Kumamoto, Shigenobu Yonemura, Akihito Inoko, Shotaro Yamano, Hideki Wanibuchi, Dongwei He, Naoki Goshima, Tohru Kiyono, Shinji Hirotsune, Masaki Inagaki. Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein-Aurora A pathway. The Journal of cell biology. 2016 Feb 15;212(4):409-23