Cargando…
Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein–Aurora A pathway
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, lo...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754717/ https://www.ncbi.nlm.nih.gov/pubmed/26880200 http://dx.doi.org/10.1083/jcb.201507046 |
_version_ | 1782416072726544384 |
---|---|
author | Inaba, Hironori Goto, Hidemasa Kasahara, Kousuke Kumamoto, Kanako Yonemura, Shigenobu Inoko, Akihito Yamano, Shotaro Wanibuchi, Hideki He, Dongwei Goshima, Naoki Kiyono, Tohru Hirotsune, Shinji Inagaki, Masaki |
author_facet | Inaba, Hironori Goto, Hidemasa Kasahara, Kousuke Kumamoto, Kanako Yonemura, Shigenobu Inoko, Akihito Yamano, Shotaro Wanibuchi, Hideki He, Dongwei Goshima, Naoki Kiyono, Tohru Hirotsune, Shinji Inagaki, Masaki |
author_sort | Inaba, Hironori |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4754717 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-47547172016-08-15 Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein–Aurora A pathway Inaba, Hironori Goto, Hidemasa Kasahara, Kousuke Kumamoto, Kanako Yonemura, Shigenobu Inoko, Akihito Yamano, Shotaro Wanibuchi, Hideki He, Dongwei Goshima, Naoki Kiyono, Tohru Hirotsune, Shinji Inagaki, Masaki J Cell Biol Research Articles 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. The Rockefeller University Press 2016-02-15 /pmc/articles/PMC4754717/ /pubmed/26880200 http://dx.doi.org/10.1083/jcb.201507046 Text en © 2016 Inaba et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Inaba, Hironori Goto, Hidemasa Kasahara, Kousuke Kumamoto, Kanako Yonemura, Shigenobu Inoko, Akihito Yamano, Shotaro Wanibuchi, Hideki He, Dongwei Goshima, Naoki Kiyono, Tohru Hirotsune, Shinji Inagaki, Masaki Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein–Aurora A pathway |
title | Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein–Aurora A pathway |
title_full | Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein–Aurora A pathway |
title_fullStr | Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein–Aurora A pathway |
title_full_unstemmed | Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein–Aurora A pathway |
title_short | Ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein–Aurora A pathway |
title_sort | ndel1 suppresses ciliogenesis in proliferating cells by regulating the trichoplein–aurora a pathway |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754717/ https://www.ncbi.nlm.nih.gov/pubmed/26880200 http://dx.doi.org/10.1083/jcb.201507046 |
work_keys_str_mv | AT inabahironori ndel1suppressesciliogenesisinproliferatingcellsbyregulatingthetrichopleinauroraapathway AT gotohidemasa ndel1suppressesciliogenesisinproliferatingcellsbyregulatingthetrichopleinauroraapathway AT kasaharakousuke ndel1suppressesciliogenesisinproliferatingcellsbyregulatingthetrichopleinauroraapathway AT kumamotokanako ndel1suppressesciliogenesisinproliferatingcellsbyregulatingthetrichopleinauroraapathway AT yonemurashigenobu ndel1suppressesciliogenesisinproliferatingcellsbyregulatingthetrichopleinauroraapathway AT inokoakihito ndel1suppressesciliogenesisinproliferatingcellsbyregulatingthetrichopleinauroraapathway AT yamanoshotaro ndel1suppressesciliogenesisinproliferatingcellsbyregulatingthetrichopleinauroraapathway AT wanibuchihideki ndel1suppressesciliogenesisinproliferatingcellsbyregulatingthetrichopleinauroraapathway AT hedongwei ndel1suppressesciliogenesisinproliferatingcellsbyregulatingthetrichopleinauroraapathway AT goshimanaoki ndel1suppressesciliogenesisinproliferatingcellsbyregulatingthetrichopleinauroraapathway AT kiyonotohru ndel1suppressesciliogenesisinproliferatingcellsbyregulatingthetrichopleinauroraapathway AT hirotsuneshinji ndel1suppressesciliogenesisinproliferatingcellsbyregulatingthetrichopleinauroraapathway AT inagakimasaki ndel1suppressesciliogenesisinproliferatingcellsbyregulatingthetrichopleinauroraapathway |