TY - JOUR
T1 - Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein-Aurora A pathway
AU - Inaba, Hironori
AU - Goto, Hidemasa
AU - Kasahara, Kousuke
AU - Kumamoto, Kanako
AU - Yonemura, Shigenobu
AU - Inoko, Akihito
AU - Yamano, Shotaro
AU - Wanibuchi, Hideki
AU - He, Dongwei
AU - Goshima, Naoki
AU - Kiyono, Tohru
AU - Hirotsune, Shinji
AU - Inagaki, Masaki
N1 - Publisher Copyright:
© 2016 Newell-Litwa.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.201507046
DO - 10.1083/jcb.201507046
M3 - Article
C2 - 26880200
AN - SCOPUS:84959468418
SN - 0021-9525
VL - 212
SP - 409
EP - 423
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 4
ER -