Despite myriad challenges, clinicians see room for progress.
Image credit: Shutterstock/David Tadevosian.
New Research In
Physical Sciences
Featured Portals
Articles by Topic
Biological Sciences
Featured Portals
Articles by Topic
Edited by Ronald D. Vale, Howard Hughes Medical Institute and University of California, San Francisco, CA, and approved February 9, 2016 (received for review August 19, 2015)
Significance
During cell division, molecular motors from the kinesin superfamily, in particular Kinesin-12 (Kif15) and Kinesin-5 (Eg5), play a crucial role in formation of the spindle—a bipolar microtubule array that is essential for accurate chromosome segregation. While Eg5 is well studied, the mechanism by which Kif15 maintains spindle bipolarity in the absence of Eg5 is unknown. In this work we reconstitute Kif15 motors on dynamic microtubules in vitro. We reveal that Kif15 is a multi-function motor that cross-links microtubules and drives transport of one along the other, which results in the formation of parallel microtubule bundles. Additionally, motors track the microtubule tips, maintaining them in a growing state, which can synchronize microtubule dynamics within a bundle.
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.
Footnotes
- ↵1To whom correspondence may be addressed. Email: a.d.mcainsh{at}warwick.ac.uk or h.drechsler{at}warwick.ac.uk.
Author contributions: H.D. and A.D.M. designed research; H.D. performed research; H.D. analyzed data; and H.D. and A.D.M. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1516370113/-/DCSupplemental.
Freely available online through the PNAS open access option.
Microtubule sorting by Kinesin-12 Kif15
Sign up for Article Alerts
Article Classifications
- Biological Sciences
- Biochemistry
Jump to section
You May Also be Interested in
Better explicating the strengths and shortcomings of these models will help refine projections and improve transparency in the years ahead.
Image credit: Witsawat.S.
Using CRISPR, researchers showed that a region some used to label “junk DNA” has a major role in a rare genetic disorder.
Image credit: Nathan Devery.
Mara Reed and Michael Manga explore why Yellowstone's Steamboat Geyser resumed erupting in 2018.
Some songbird parents might improve their own fitness by manipulating their offspring into leaving the nest early, at the cost of fledgling survival, a study finds.
Image credit: Gil Eckrich (photographer).