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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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Bibliographic Details
Published in:Cell reports (Cambridge) 2015-02, Vol.10 (5), p.664-673
Main Authors: Miyamoto, Tatsuo, Hosoba, Kosuke, Ochiai, Hiroshi, Royba, Ekaterina, Izumi, Hideki, Sakuma, Tetsushi, Yamamoto, Takashi, Dynlacht, Brian David, Matsuura, Shinya
Format: Article
Language:English
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Summary: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. [Display omitted] •KIF2A is required for primary cilia disassembly•PLK1 phosphorylates KIF2A to enhance microtubule-depolymerizing activity•KIF2A is quantitatively controlled by APC/C ubiquitin ligase•Constitutive activation of PLK1-KIF2A pathway impairs ciliogenesis Primary cilium disassembly is coupled with cell proliferation. Miyamoto et al. now find that the PLK1-KIF2A pathway drives physiological cilia disassembly and that its constitutive activation contributes to defective ciliogenesis in PCS syndrome caused by mutation of the BubR1 gene.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2015.01.003