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...

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Main Authors: Weiping Wang, Tao Wu, Marc W Kirschner
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2014-08-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/03083
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spelling doaj-81ec39744a044a1695a9591637a4d5f92021-05-04T23:25:17ZengeLife Sciences Publications LtdeLife2050-084X2014-08-01310.7554/eLife.03083The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary ciliumWeiping Wang0Tao Wu1Marc W Kirschner2Department of Systems Biology, Harvard Medical School, Boston, United StatesDepartment of Systems Biology, Harvard Medical School, Boston, United StatesDepartment of Systems Biology, Harvard Medical School, Boston, United StatesThe 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.https://elifesciences.org/articles/03083primary cilumubiquitincell cycleretinal cell culture
collection DOAJ
language English
format Article
sources DOAJ
author Weiping Wang
Tao Wu
Marc W Kirschner
spellingShingle Weiping Wang
Tao Wu
Marc W Kirschner
The master cell cycle regulator APC-Cdc20 regulates ciliary length and disassembly of the primary cilium
eLife
primary cilum
ubiquitin
cell cycle
retinal cell culture
author_facet Weiping Wang
Tao Wu
Marc W Kirschner
author_sort Weiping Wang
title 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_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_sort master cell cycle regulator apc-cdc20 regulates ciliary length and disassembly of the primary cilium
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2014-08-01
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.
topic primary cilum
ubiquitin
cell cycle
retinal cell culture
url https://elifesciences.org/articles/03083
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