title: Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein-Aurora A pathway.
abstract: 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.
authors.affiliation: Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Inaba
authors.affiliation: Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan Department of Cellular Oncology, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan.
authors.forename: Hidemasa
authors.initials: H
authors.lastname: Goto
authors.affiliation: Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan Department of Oncology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8601, Japan.
authors.forename: Kousuke
authors.initials: K
authors.lastname: Kasahara
authors.affiliation: Department of Genetic Disease Research, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Kumamoto
authors.affiliation: Center for Life Science Technologies (Ultrastructural Research Team), Institute of Physical and Chemical Research, Kobe 650-0047, Japan.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Yonemura
authors.affiliation: Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Inoko
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Yamano
authors.affiliation: Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
authors.affiliation: Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
authors.forename: Dongwei
authors.initials: D
authors.lastname: He
authors.affiliation: Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Tokyo 135-0064, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Goshima
authors.affiliation: Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tokyo 104-0045, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Kiyono
authors.affiliation: Department of Genetic Disease Research, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Hirotsune
authors.affiliation: Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan Department of Cellular Oncology, Graduate School of Medicine, Nagoya University, Nagoya 466-8550, Japan minagaki@aichi-cc.jp.
authors.forename: Masaki
authors.initials: M
authors.lastname: Inagaki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D064096:Aurora Kinase A / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D049109:Cell Proliferation; D002502:Centrioles / Q000201:enzymology; D002923:Cilia / Q000201:enzymology; D004847:Epithelial Cells / Q000201:enzymology*; D005838:Genotype; D006367:HeLa Cells; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000201:enzymology; D010641:Phenotype; D055550:Protein Stability; D059748:Proteolysis; D034622:RNA Interference; D015398:Signal Transduction; D041701:Swiss 3T3 Cells; D013997:Time Factors; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C000600308:KCTD17 protein, human; C421108:NDEL1 protein, human; C486015:Ndel1 protein, mouse; C502303:TCHP protein, human; C576917:AURKA protein, human; C576918:Aurka protein, mouse; D064096:Aurora Kinase A