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Molecular and Cellular Biology, December 2008, p. 7199-7211, Vol. 28, No. 23
0270-7306/08/$08.00+0     doi:10.1128/MCB.01040-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

MCAK-Independent Functions of ch-Tog/XMAP215 in Microtubule Plus-End Dynamics{triangledown} ,{dagger}

Alexis R. Barr1,2 and Fanni Gergely1,2*

Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, United Kingdom,1 Department of Oncology, University of Cambridge, Cambridge, United Kingdom2

Received 2 July 2008/ Returned for modification 2 August 2008/ Accepted 14 September 2008

The formation of a functional bipolar mitotic spindle is essential for genetic integrity. In human cells, the microtubule polymerase XMAP215/ch-Tog ensures spindle bipolarity by counteracting the activity of the microtubule-depolymerizing kinesin XKCM1/MCAK. Their antagonistic effects on microtubule polymerization confer dynamic instability on microtubules assembled in cell-free systems. It is, however, unclear if a similar interplay governs microtubule behavior in mammalian cells in vivo. Using real-time analysis of spindle assembly, we found that ch-Tog is required to produce or maintain long centrosomal microtubules after nuclear-envelope breakdown. In the absence of ch-Tog, microtubule assembly at centrosomes was impaired and microtubules were nondynamic. Interkinetochore distances and the lengths of kinetochore fibers were also reduced in these cells. Codepleting MCAK with ch-Tog improved kinetochore fiber length and interkinetochore separation but, surprisingly, did not rescue centrosomal microtubule assembly and microtubule dynamics. Our data therefore suggest that ch-Tog has at least two distinct roles in spindle formation. First, it protects kinetochore microtubules from depolymerization by MCAK. Second, ch-Tog plays an essential role in centrosomal microtubule assembly, a function independent of MCAK activity. Thus, the notion that the antagonistic activities of MCAK and ch-Tog determine overall microtubule stability is too simplistic to apply to human cells.

* Corresponding author. Mailing address: Cancer Research UK Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, United Kingdom. Phone: 44-1223-404280. Fax: 44-1223-404573. E-mail: Fanni.Gergely{at}cancer.org.uk

{triangledown} Published ahead of print on 22 September 2008.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, December 2008, p. 7199-7211, Vol. 28, No. 23
0270-7306/08/$08.00+0     doi:10.1128/MCB.01040-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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