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Kinesin-12 motors cooperate to suppress microtubule catastrophes and drive the formation of parallel microtubule bundles
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Drechsler, Hauke and McAinsh, Andrew D. (2016) Kinesin-12 motors cooperate to suppress microtubule catastrophes and drive the formation of parallel microtubule bundles. Proceedings of the National Academy of Sciences of the United States of America, 113 (12). E1635-E1644. doi:10.1073/pnas.1516370113 ISSN 0027-8424.
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Official URL: http://dx.doi.org/10.1073/pnas.1516370113
Abstract
Human Kinesin-12 (hKif15) plays a crucial role in assembly and maintenance of the mitotic spindle. These functions of hKif15 are partially redundant with Kinesin-5 (Eg5), which can cross-link and drive the extensile sliding of antiparallel microtubules. Although both motors are known to be tetramers, the functional properties of hKif15 are less well understood. Here we reveal how single or multiple Kif15 motors can cross-link, transport, and focus the plus-ends of intersecting microtubules. During transport, Kif15 motors step simultaneously along both microtubules with relative microtubule transport driven by a velocity differential between motor domain pairs. Remarkably, this differential is affected by the underlying intersection geometry: the differential is low on parallel and extreme on antiparallel microtubules where one motor domain pair becomes immobile. As a result, when intersecting microtubules are antiparallel, canonical transport of one microtubule along the other is allowed because one motor is firmly attached to one microtubule while it is stepping on the other. When intersecting microtubules are parallel, however, Kif15 motors can drive (biased) parallel sliding because the motor simultaneously steps on both microtubules that it cross-links. These microtubule rearrangements will focus microtubule plus-ends and finally lead to the formation of parallel bundles. At the same time, Kif15 motors cooperate to suppress catastrophe events at polymerizing microtubule plus-ends, raising the possibility that Kif15 motors may synchronize the dynamics of bundles that they have assembled. Thus, Kif15 is adapted to operate on parallel microtubule substrates, a property that clearly distinguishes it from the other tetrameric spindle motor, Eg5.
| Item Type: | Journal Article | ||||||||
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| Subjects: | Q Science > Q Science (General) | ||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | Proceedings of the National Academy of Sciences of the United States of America | ||||||||
| Publisher: | National Academy of Sciences | ||||||||
| ISSN: | 0027-8424 | ||||||||
| Official Date: | 22 March 2016 | ||||||||
| Dates: |
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| Volume: | 113 | ||||||||
| Number: | 12 | ||||||||
| Page Range: | E1635-E1644 | ||||||||
| DOI: | 10.1073/pnas.1516370113 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||
| Date of first compliant deposit: | 15 January 2017 | ||||||||
| Open Access Version: |
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