Depolymerizing kinesins Kip3 and MCAK shape cellular microtubule architecture by differential control of catastrophe

Melissa K. Gardner, Marija Zanic, Christopher Gell, Volker Bormuth, Jonathon Howard

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125 Scopus citations

Abstract

Microtubules are dynamic filaments whose ends alternate between periods of slow growth and rapid shortening as they explore intracellular space and move organelles. A key question is how regulatory proteins modulate catastrophe, the conversion from growth to shortening. To study this process, we reconstituted microtubule dynamics in the absence and presence of the kinesin-8 Kip3 and the kinesin-13 MCAK. Surprisingly, we found that, even in the absence of the kinesins, the microtubule catastrophe frequency depends on the age of the microtubule, indicating that catastrophe is a multistep process. Kip3 slowed microtubule growth in a length-dependent manner and increased the rate of aging. In contrast, MCAK eliminated the aging process. Thus, both kinesins are catastrophe factors; Kip3 mediates fine control of microtubule length by narrowing the distribution of maximum lengths prior to catastrophe, whereas MCAK promotes rapid restructuring of the microtubule cytoskeleton by making catastrophe a first-order random process.

Original languageEnglish (US)
Pages (from-to)1092-1103
Number of pages12
JournalCell
Volume147
Issue number5
DOIs
StatePublished - Nov 23 2011

Bibliographical note

Funding Information:
The authors thank members of the Howard Laboratory, in particular the Muffins Group, for advice and assistance. We thank Dr. V. Varga and Dr. C. Friel for protein and advice. M.K.G. was supported by a Whitaker International Scholar Fellowship, M.Z. by a Cross-Disciplinary Fellowship from the International Human Frontier Science Program Organization, and V.B. by a fellowship from the Boehringer Ingelheim Fonds.

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