Cargando…
The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium
The primary cilium has an important role in signaling; defects in structure are associated with a variety of human diseases. Much of the most basic biology of this organelle is poorly understood, even basic mechanisms, such as control of growth and resorption. We show that the activity of the anapha...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135350/ https://www.ncbi.nlm.nih.gov/pubmed/25139956 http://dx.doi.org/10.7554/eLife.03083 |
_version_ | 1782330983401390080 |
---|---|
author | Wang, Weiping Wu, Tao Kirschner, Marc W |
author_facet | Wang, Weiping Wu, Tao Kirschner, Marc W |
author_sort | Wang, Weiping |
collection | PubMed |
description | The primary cilium has an important role in signaling; defects in structure are associated with a variety of human diseases. Much of the most basic biology of this organelle is poorly understood, even basic mechanisms, such as control of growth and resorption. We show that the activity of the anaphase-promoting complex (APC), an E3 that regulates the onset of anaphase, destabilizes axonemal microtubules in the primary cilium. Furthermore, the metaphase APC co-activator, Cdc20, is specifically recruited to the basal body of primary cilia. Inhibition of APC-Cdc20 activity increases the ciliary length, while overexpression of Cdc20 suppresses cilium formation. APC-Cdc20 activity is required for the timely resorption of the cilium after serum stimulation. In addition, APC regulates the stability of axonemal microtubules through targeting Nek1, the ciliary kinase, for proteolysis. These data demonstrate a novel function of APC beyond cell cycle control and implicate critical role of ubiquitin-mediated proteolysis in ciliary disassembly. DOI: http://dx.doi.org/10.7554/eLife.03083.001 |
format | Online Article Text |
id | pubmed-4135350 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-41353502014-08-22 The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium Wang, Weiping Wu, Tao Kirschner, Marc W eLife Cell Biology The primary cilium has an important role in signaling; defects in structure are associated with a variety of human diseases. Much of the most basic biology of this organelle is poorly understood, even basic mechanisms, such as control of growth and resorption. We show that the activity of the anaphase-promoting complex (APC), an E3 that regulates the onset of anaphase, destabilizes axonemal microtubules in the primary cilium. Furthermore, the metaphase APC co-activator, Cdc20, is specifically recruited to the basal body of primary cilia. Inhibition of APC-Cdc20 activity increases the ciliary length, while overexpression of Cdc20 suppresses cilium formation. APC-Cdc20 activity is required for the timely resorption of the cilium after serum stimulation. In addition, APC regulates the stability of axonemal microtubules through targeting Nek1, the ciliary kinase, for proteolysis. These data demonstrate a novel function of APC beyond cell cycle control and implicate critical role of ubiquitin-mediated proteolysis in ciliary disassembly. DOI: http://dx.doi.org/10.7554/eLife.03083.001 eLife Sciences Publications, Ltd 2014-08-19 /pmc/articles/PMC4135350/ /pubmed/25139956 http://dx.doi.org/10.7554/eLife.03083 Text en Copyright © 2014, Wang et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cell Biology Wang, Weiping Wu, Tao Kirschner, Marc W The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium |
title | The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium |
title_full | The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium |
title_fullStr | The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium |
title_full_unstemmed | The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium |
title_short | The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium |
title_sort | master cell cycle regulator apc-cdc20 regulates ciliary length and disassembly of the primary cilium |
topic | Cell Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4135350/ https://www.ncbi.nlm.nih.gov/pubmed/25139956 http://dx.doi.org/10.7554/eLife.03083 |
work_keys_str_mv | AT wangweiping themastercellcycleregulatorapccdc20regulatesciliarylengthanddisassemblyoftheprimarycilium AT wutao themastercellcycleregulatorapccdc20regulatesciliarylengthanddisassemblyoftheprimarycilium AT kirschnermarcw themastercellcycleregulatorapccdc20regulatesciliarylengthanddisassemblyoftheprimarycilium AT wangweiping mastercellcycleregulatorapccdc20regulatesciliarylengthanddisassemblyoftheprimarycilium AT wutao mastercellcycleregulatorapccdc20regulatesciliarylengthanddisassemblyoftheprimarycilium AT kirschnermarcw mastercellcycleregulatorapccdc20regulatesciliarylengthanddisassemblyoftheprimarycilium |