Prime movers: the mechanochemistry of mitotic kinesins

Cross, Robert A.; McAinsh, Andrew D.

doi:10.1038/nrm3768

Cited by 177 publications

(205 citation statements)

References 186 publications

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“…1,2 Chromosome movements during congression are driven by 2 main mechanisms: microtubule polymerization/depolymerization-based motion 3 and motor-dependent transport along microtubules. [4][5][6] The latter is mainly achieved through the coordinated activities of cytoplasmic Dynein, CENP-E and chromokinesins. 5 Cytoplasmic Dynein (from here on referred as Dynein) is a large protein complex (1.6 MDa) consisting of several subunits: 2 heavy chains containing ATPase motor domains, 2 intermediate chains, 2 light intermediate chains and 3 different types of light chains.…”

Section: Introductionmentioning

confidence: 99%

Dynein prevents erroneous kinetochore-microtubule attachments in mitosis

Barišić

Maiato

2015

Cell Cycle

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Section: Introductionmentioning

confidence: 99%

Dynein prevents erroneous kinetochore-microtubule attachments in mitosis

Barišić

Maiato

2015

Cell Cycle

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“…Following assembly, the spindle must be maintained in a bipolar state before being remodeled throughout anaphase and cytokinesis. These events are contingent on the dynamic nature of microtubules and multiple force-generating molecular motors (1). The initial step in spindle assembly involves the separation of the duplicated centrosomes during prophase (2).…”

mentioning

confidence: 99%

Kinesin-12 motors cooperate to suppress microtubule catastrophes and drive the formation of parallel microtubule bundles

Drechsler

McAinsh

2016

Proc. Natl. Acad. Sci. U.S.A.

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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 plusends 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.Kinesin-12 | Kif15 | mitosis | mitotic spindle

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“…The minus-end directed C-terminal kinesin-14, ncd, is such a nonprocessive motor. It has been shown to play an essential role in spindle focusing (9)(10)(11) and to slide and cross-link microtubules (12,13).…”

mentioning

confidence: 99%

Working stroke of the kinesin-14, ncd, comprises two substeps of different direction

Nitzsche

Dudek

Hajdo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Single-molecule experiments have been used with great success to explore the mechanochemical cycles of processive motor proteins such as kinesin-1, but it has proven difficult to apply these approaches to nonprocessive motors. Therefore, the mechanochemical cycle of kinesin-14 (ncd) is still under debate. Here, we use the readout from the collective activity of multiple motors to derive information about the mechanochemical cycle of individual ncd motors. In gliding motility assays we performed 3D imaging based on fluorescence interference contrast microscopy combined with nanometer tracking to simultaneously study the translation and rotation of microtubules. Microtubules gliding on ncd-coated surfaces rotated around their longitudinal axes in an [ATP]-and [ADP]-dependent manner. Combined with a simple mechanical model, these observations suggest that the working stroke of ncd consists of an initial small movement of its stalk in a lateral direction when ADP is released and a second, main component of the working stroke, in a longitudinal direction upon ATP binding.kinesin | microtubule | gliding motility assay | fluorescence interference contrast microscopy | mathematical modeling S ingle-molecule techniques, in particular single-molecule fluorescence (1) and optical tweezers (2), have greatly advanced our understanding of motor proteins. Such experiments normally rely on the processivity of the motor, which makes it possible to observe multiple consecutive working cycles (i.e., steps). Although single-molecule mechanical measurements on nonprocessive motors can be performed with optical tweezers (3, 4), they require a sophisticated statistical analysis (5, 6) and, if the motor is to be studied under load, advanced feedback (7) or force-clamp mechanisms (8). The minus-end directed C-terminal kinesin-14, ncd, is such a nonprocessive motor. It has been shown to play an essential role in spindle focusing (9-11) and to slide and cross-link microtubules (12, 13).For the working stroke of a single ncd motor a lever arm model has been suggested (14, 15). However, as reviewed in ref. 16 the triggering event for the working stroke is still under debate. On the one hand, it has been suggested that the working stroke is connected to the ADP release (14, 17). On the other hand, it has been proposed to be coupled to the binding of ATP to the microtubule (MT)-ncd complex (4,15,18). In another study, a twostage displacement of the ncd stalk has been proposed where stalk displacement is initiated by binding of ncd to the MT and completed upon ATP binding (19). However, even though a variety of approaches including X-ray crystallography (15), EM (20-23), optical trapping (4, 24), FRET (19), and computational modeling (25) have been used to study the coupling between nucleotide states and mechanical states of ncd, the exact mechanism remains to be elucidated.Alternatively, nonprocessive motors can be studied in gliding motility assays (26) albeit with the disadvantage that single-motor behavior is difficult to access. On an ncd...

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Prime movers: the mechanochemistry of mitotic kinesins

Cited by 177 publications

References 186 publications

Dynein prevents erroneous kinetochore-microtubule attachments in mitosis

Dynein prevents erroneous kinetochore-microtubule attachments in mitosis

Kinesin-12 motors cooperate to suppress microtubule catastrophes and drive the formation of parallel microtubule bundles

Working stroke of the kinesin-14, ncd, comprises two substeps of different direction

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