Nonautonomous Movement of Chromosomes in Mitosis

Vladimirou, Elina; Mchedlishvili, Nunu; Gasic, Ivana; Armond, Jonathan W.; Samora, Catarina P.; Meraldi, Patrick; McAinsh, Andrew D.

doi:10.1016/j.devcel.2013.08.004

Cited by 57 publications

(65 citation statements)

References 53 publications

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“…Similarly, a previous study has shown that neighboring kinetochore pairs oscillate in a correlated manner, which was explained by elastic linkages between k‐fibers 37. Our results support the existence of lateral connections between adjacent bundles consisting of bridging and k‐fibers.…”

Section: Resultssupporting

confidence: 91%

PRC 1‐labeled microtubule bundles and kinetochore pairs show one‐to‐one association in metaphase

et al. 2016

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In the mitotic spindle, kinetochore microtubules form k‐fibers, whereas overlap or interpolar microtubules form antiparallel arrays containing the cross‐linker protein regulator of cytokinesis 1 (PRC1). We have recently shown that an overlap bundle, termed bridging fiber, links outermost sister k‐fibers. However, the relationship between overlap bundles and k‐fibers throughout the spindle remained unknown. Here, we show that in a metaphase spindle more than 90% of overlap bundles act as a bridge between sister k‐fibers. We found that the number of PRC1‐GFP‐labeled bundles per spindle is nearly the same as the number of kinetochore pairs. Live‐cell imaging revealed that kinetochore movement in the equatorial plane of the spindle is highly correlated with the movement of the coupled PRC1‐GFP‐labeled fiber, whereas the correlation with other fibers decreases with increasing distance. Analysis of endogenous PRC1 localization confirmed the results obtained with PRC1‐GFP. PRC1 knockdown reduced the bridging fiber thickness and interkinetochore distance throughout the spindle, suggesting a function of PRC1 in bridging microtubule organization and force balance in the metaphase spindle.

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Section: Resultssupporting

confidence: 91%

PRC 1‐labeled microtubule bundles and kinetochore pairs show one‐to‐one association in metaphase

et al. 2016

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“…Like that, it is possible that hKif15 would contribute to the control of microtubule plus-end dynamics at the kinetochore; in this regard hKif15 has also been reported to localize to kinetochores (11) and influence chromosome movement (21). Promoting microtubule growth in the kinetochore fiber can indirectly create outwardpushing forces on the centrosome to assist spindle elongation.…”

Section: Discussionmentioning

confidence: 99%

“…In human cells, hKif15 is largely localized to parallel microtubule bundles (11,21). Thus, it might be possible that hKif15 uses geometry-dependent transport and (biased) parallel sliding to autonomously drive formation of parallel bundles.…”

Section: Kif15 Motors Can Only Translocate On Two Microtubules Simultmentioning

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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“…KIF23 was recently found to be the gene mutated in families with CDA type III. 9,54 Thus, there is a direct genetic link between KLF1 and CDA types IV and III. There are other novel KLF1 target genes that may be important for regulating mitosis including TRIB3, which controls cell division in response to erythropoietin.…”

Section: Klf1 Regulates the Cell Cycle And Mitosismentioning

confidence: 99%

KLF1-null neonates display hydrops fetalis and a deranged erythroid transcriptome

Magor

Tallack

Gillinder

et al. 2015

Blood

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Key Points• Complete loss of KLF1 function is compatible with life but results in severe nonspherocytic hemolytic anemia and kernicterus.• Human KLF1 regulates most aspects of red cell biology.We describe a case of severe neonatal anemia with kernicterus caused by compound heterozygosity for null mutations in KLF1, each inherited from asymptomatic parents. One of the mutations is novel. This is the first described case of a KLF1-null human. The phenotype of severe nonspherocytic hemolytic anemia, jaundice, hepatosplenomegaly, and marked erythroblastosis is more severe than that present in congenital dyserythropoietic anemia type IV as a result of dominant mutations in the second zinc-finger of KLF1. There was a very high level of HbF expression into childhood (>70%), consistent with a key role for KLF1 in human hemoglobin switching. We performed RNA-seq on circulating erythroblasts and found that human KLF1 acts like mouse Klf1 to coordinate expression of many genes required to build a red cell including those encoding globins, cytoskeletal components, AHSP, heme synthesis enzymes, cell-cycle regulators, and blood group antigens. We identify novel KLF1 target genes including KIF23 and KIF11 which are required for proper cytokinesis. We also identify new roles for KLF1 in autophagy, global transcriptional control, and RNA splicing. We suggest loss of KLF1 should be considered in otherwise unexplained cases of severe neonatal NSHA or hydrops fetalis. (Blood. 2015;125(15):2405-2417

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Nonautonomous Movement of Chromosomes in Mitosis

Cited by 57 publications

References 53 publications

PRC 1‐labeled microtubule bundles and kinetochore pairs show one‐to‐one association in metaphase

PRC 1‐labeled microtubule bundles and kinetochore pairs show one‐to‐one association in metaphase

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

KLF1-null neonates display hydrops fetalis and a deranged erythroid transcriptome

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