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The Microtubule-Depolymerizing Activity of a Mitotic Kinesin Protein KIF2A Drives Primary Cilia Disassembly Coupled with Cell Proliferation

The primary cilium is an antenna-like, microtubule-based organelle on the surface of most vertebrate cells for receiving extracellular information. Although primary cilia form in the quiescent phase, ciliary disassembly occurs when quiescent cells re-enter the proliferative phase. It was shown that...

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Autores principales: Miyamoto, Tatsuo, Hosoba, Kosuke, Ochiai, Hiroshi, Royba, Ekaterina, Izumi, Hideki, Sakuma, Tetsushi, Yamamoto, Takashi, Dynlacht, Brian David, Matsuura, Shinya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099117/
https://www.ncbi.nlm.nih.gov/pubmed/25660017
http://dx.doi.org/10.1016/j.celrep.2015.01.003
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author Miyamoto, Tatsuo
Hosoba, Kosuke
Ochiai, Hiroshi
Royba, Ekaterina
Izumi, Hideki
Sakuma, Tetsushi
Yamamoto, Takashi
Dynlacht, Brian David
Matsuura, Shinya
author_facet Miyamoto, Tatsuo
Hosoba, Kosuke
Ochiai, Hiroshi
Royba, Ekaterina
Izumi, Hideki
Sakuma, Tetsushi
Yamamoto, Takashi
Dynlacht, Brian David
Matsuura, Shinya
author_sort Miyamoto, Tatsuo
collection PubMed
description The primary cilium is an antenna-like, microtubule-based organelle on the surface of most vertebrate cells for receiving extracellular information. Although primary cilia form in the quiescent phase, ciliary disassembly occurs when quiescent cells re-enter the proliferative phase. It was shown that a mitotic kinase, Polo-like kinase 1 (PLK1), is required for cell-proliferation-coupled primary cilia disassembly. Here, we report that kinesin superfamily protein 2A (KIF2A), phosphorylated at T554 by PLK1, exhibits microtubule-depolymerizing activity at the mother centriole to disassemble the primary cilium in a growth-signal-dependent manner. KIF2A-deficient hTERT-RPE1 cells showed the impairment of primary cilia disassembly following growth stimulation. It was also found that the PLK1-KIF2A pathway is constitutively active in cells from patients with premature chromatid separation (PCS) syndrome and is responsible for defective ciliogenesis in this syndrome. These findings provide insights into the roles of the PLK1-KIF2A pathway in physiological cilia disassembly and cilia-associated disorders.
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spelling pubmed-50991172016-11-07 The Microtubule-Depolymerizing Activity of a Mitotic Kinesin Protein KIF2A Drives Primary Cilia Disassembly Coupled with Cell Proliferation Miyamoto, Tatsuo Hosoba, Kosuke Ochiai, Hiroshi Royba, Ekaterina Izumi, Hideki Sakuma, Tetsushi Yamamoto, Takashi Dynlacht, Brian David Matsuura, Shinya Cell Rep Article The primary cilium is an antenna-like, microtubule-based organelle on the surface of most vertebrate cells for receiving extracellular information. Although primary cilia form in the quiescent phase, ciliary disassembly occurs when quiescent cells re-enter the proliferative phase. It was shown that a mitotic kinase, Polo-like kinase 1 (PLK1), is required for cell-proliferation-coupled primary cilia disassembly. Here, we report that kinesin superfamily protein 2A (KIF2A), phosphorylated at T554 by PLK1, exhibits microtubule-depolymerizing activity at the mother centriole to disassemble the primary cilium in a growth-signal-dependent manner. KIF2A-deficient hTERT-RPE1 cells showed the impairment of primary cilia disassembly following growth stimulation. It was also found that the PLK1-KIF2A pathway is constitutively active in cells from patients with premature chromatid separation (PCS) syndrome and is responsible for defective ciliogenesis in this syndrome. These findings provide insights into the roles of the PLK1-KIF2A pathway in physiological cilia disassembly and cilia-associated disorders. 2015-02-05 2015-02-10 /pmc/articles/PMC5099117/ /pubmed/25660017 http://dx.doi.org/10.1016/j.celrep.2015.01.003 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
spellingShingle Article
Miyamoto, Tatsuo
Hosoba, Kosuke
Ochiai, Hiroshi
Royba, Ekaterina
Izumi, Hideki
Sakuma, Tetsushi
Yamamoto, Takashi
Dynlacht, Brian David
Matsuura, Shinya
The Microtubule-Depolymerizing Activity of a Mitotic Kinesin Protein KIF2A Drives Primary Cilia Disassembly Coupled with Cell Proliferation
title The Microtubule-Depolymerizing Activity of a Mitotic Kinesin Protein KIF2A Drives Primary Cilia Disassembly Coupled with Cell Proliferation
title_full The Microtubule-Depolymerizing Activity of a Mitotic Kinesin Protein KIF2A Drives Primary Cilia Disassembly Coupled with Cell Proliferation
title_fullStr The Microtubule-Depolymerizing Activity of a Mitotic Kinesin Protein KIF2A Drives Primary Cilia Disassembly Coupled with Cell Proliferation
title_full_unstemmed The Microtubule-Depolymerizing Activity of a Mitotic Kinesin Protein KIF2A Drives Primary Cilia Disassembly Coupled with Cell Proliferation
title_short The Microtubule-Depolymerizing Activity of a Mitotic Kinesin Protein KIF2A Drives Primary Cilia Disassembly Coupled with Cell Proliferation
title_sort microtubule-depolymerizing activity of a mitotic kinesin protein kif2a drives primary cilia disassembly coupled with cell proliferation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5099117/
https://www.ncbi.nlm.nih.gov/pubmed/25660017
http://dx.doi.org/10.1016/j.celrep.2015.01.003
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