Force on spindle microtubule minus ends moves chromosomes

Elting, Mary Williard; Hueschen, Christina L.; Udy, Dylan B.; Dumont, Sophie

doi:10.1083/jcb.201401091

Cited by 124 publications

(219 citation statements)

References 54 publications

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“…Minus-end position data ( Figure 3C) were generated by manual tracking of ablation-created k-fiber minus-ends (marked by GFP-CAMSAP1) and spindle poles in time-lapse videos, using a second homewritten Matlab program (Elting et al, 2014). Nearest neighbor distances between NuMA puncta in STORM imaging ( Figure 5H) were measured as the center-to-center distance from each NuMA puncta to its nearest neighboring puncta.…”

Section: Discussionmentioning

confidence: 99%

“…Live confocal imaging of a PtK2 cell expressing GFP-Arp1A, with spindle microtubules labeled by siR-tubulin. GFPArp1A is recruited to k-fiber minus-ends (arrowhead) created by ablation ('X') and moves with them as dynein pulls them poleward (Elting et al, 2014). Time is in min:s, with the frame captured immediately following ablation set to 00:00.…”

Section: Drug Treatment and Microtubule Re-growthmentioning

confidence: 99%

“…NuMA is required for dynein activity and dynactin localization at minusends If NuMA does target dynein-dynactin to minus-ends, localizing force there, we would expect NuMA to be required for dynein to transport minus-ends created by k-fiber ablation (Elting et al, 2014; Sikirzhytski et al, 2014). To test this hypothesis, we made inducible CRISPR/Cas9 RPE1 cell lines to knock out NuMA (Figure 3-figure supplement 1) (McKinley et al, 2015;Wang et al, 2015).…”

Section: Numa Localizes To Minus-ends Independently Of Dyneinmentioning

confidence: 99%

“…Under these conditions, there was no detected defect in spindle appearance or microtubule dynamics. As described elsewhere (Elting et al, 2014), cells were imaged using a spinning disk confocal inverted microscope (Eclipse Ti-E; Nikon Instruments, Melville, NY) with a 100 Â 1.45 Ph3 oil objective through a 1.5X lens, operated by MetaMorph (7.7.8.0; Molecular Devices, Sunnyvale, CA). Laser ablation (30 3-ns pulses at 20 Hz) with 551 nm light was performed using the galvo-controlled MicroPoint Laser System (Andor, Belfast, UK).…”

Section: Continued On Next Pagementioning

confidence: 99%

“…In computational models, localizing a minus-end-directed motor at microtubule ends permits microtubule clustering into asters or poles (Foster et al, 2015;Goshima et al, 2005;Nedelec and Surrey, 2001;Surrey et al, 2001) and the emergence of a robust steady-state spindle length (Burbank et al, 2007). More recently, experimental work has shown that dynein-dynactin and NuMA do indeed selectively localize to spindle minus-ends, with dynein pulling on them after kinetochore-fiber (k-fiber) ablation in mammalian spindles (Elting et al, 2014;Sikirzhytski et al, 2014). This is consistent with suggestions that dynein and NuMA capture and pull on distal k-fiber minus-ends in monopolar spindles (Khodjakov et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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NuMA Recruits Dynein Activity to Microtubule Minus-Ends at Mitosis

Hueschen

Kenny

et al. 2018

Biophysical Journal

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To build the spindle at mitosis, motors exert spatially regulated forces on microtubules. We know that dynein pulls on mammalian spindle microtubule minus-ends, and this localized activity at ends is predicted to allow dynein to cluster microtubules into poles. How dynein becomes enriched at minus-ends is not known. Here, we use quantitative imaging and laser ablation to show that NuMA targets dynactin to minus-ends, localizing dynein activity there. NuMA is recruited to new minus-ends independently of dynein and more quickly than dynactin; both NuMA and dynactin display specific, steady-state binding at minus-ends. NuMA localization to minus-ends involves a C-terminal region outside NuMA's canonical microtubule-binding domain and is independent of minus-end binders g-TuRC, CAMSAP1, and KANSL1/3. Both NuMA's minus-endbinding and dynein-dynactin-binding modules are required to rescue focused, bipolar spindle organization. Thus, NuMA may serve as a mitosis-specific minus-end cargo adaptor, targeting dynein activity to minus-ends to cluster spindle microtubules into poles.

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Section: Discussionmentioning

confidence: 99%

Section: Drug Treatment and Microtubule Re-growthmentioning

confidence: 99%

Section: Numa Localizes To Minus-ends Independently Of Dyneinmentioning

confidence: 99%

Section: Continued On Next Pagementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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NuMA Recruits Dynein Activity to Microtubule Minus-Ends at Mitosis

Hueschen

Kenny

et al. 2018

Biophysical Journal

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Role of Nonmotor Microtubule‐Associated Proteins in Mitotic Spindle Assembly

Drpic

Maiato

2017

Encyclopedia of Life Sciences

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The assembly of a microtubule (MT)‐based bipolar spindle is a distinct hallmark of mitosis. Mitotic spindle assembly is tightly controlled in order to ensure proper chromosome attachment and segregation during mitosis. This regulation is achieved by the coordinated action of many motor and nonmotor MT‐associated proteins (MAPs). Owing to the distinctive capacity of MAPs to associate with the MT minus and/or plus ends, as well as with the MT lattice, they play an essential role in the spatial and temporal regulation of MT behaviour during mitotic spindle assembly. Key Concepts The mitotic spindle is a dynamic structure composed of microtubules, motor and nonmotor proteins. Proper chromosome alignment and segregation during mitosis requires bipolar spindle assembly. Nonmotor microtubule‐associated proteins are involved in spindle pole focusing, microtubule dynamics, kinetochore‐microtubule attachment stability and cytokinesis. Nonmotor microtubule‐associated proteins associate with microtubule plus and minus ends (+TIPs and −TIPs, respectively) as well as with the microtubule lattice. Nonmotor microtubule‐associated proteins are tightly regulated during the cell cycle.

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Elastic tethers between separating anaphase chromosomes in crane‐fly spermatocytes coordinate chromosome movements to the two poles

2017

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Separating anaphase chromosomes in crane-fly spermatocytes are connected by elastic tethers, as originally described by LaFountain et al. (2002): telomere-containing arm fragments severed from the arms move backwards to the partner telomeres. We have tested whether the tethers coordinate the movements of separating partner chromosomes. In other cell types anaphase chromosomes move faster, temporarily, when their kinetochore microtubules are severed. However, in crane-fly spermatocytes the chromosomes move at their usual speed when their kinetochore microtubules are severed. To test whether the absence of increased velocity is because tethers link the separating chromosomes and coordinate their movements, we cut tethers with a laser microbeam and then cut the kinetochore microtubules. After this procedure, the associated chromosome sped up, as in other cells. These results indicate that the movements of partner anaphase chromosomes in crane-fly spermatocytes are coordinated by elastic tethers connecting the two chromosomes and confirm that chromosomes speed up in anaphase when their kinetochore microtubules are severed. © 2016 Wiley Periodicals, Inc.

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Force on spindle microtubule minus ends moves chromosomes

Abstract: After the loss of continuous spindle microtubule attachment to the spindle pole, a previously undescribed mechanism of chromosome transport, powered by dynein pulling on minus ends of severed microtubules, repairs spindle architecture and integrity.

Cited by 124 publications

References 54 publications

NuMA Recruits Dynein Activity to Microtubule Minus-Ends at Mitosis

NuMA Recruits Dynein Activity to Microtubule Minus-Ends at Mitosis

Role of Nonmotor Microtubule‐Associated Proteins in Mitotic Spindle Assembly

Elastic tethers between separating anaphase chromosomes in crane‐fly spermatocytes coordinate chromosome movements to the two poles

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