The lamin-B nuclear envelope stabilizes spindle microtubules by keeping the competitive motility of opposing-force kinesins in check

Brust-Mascher, Ingrid

Civelekoglu-Scholey, Gul

Scholey, Jonathan M.

Tao, Li

Wollman, Roy

English

PubMed

Crossref

We tested the classical hypothesis that astral, prometaphase bipolar mitotic spindles are maintained by balanced outward and inward forces exerted on spindle poles by kinesin-5 and -14 using modeling of in vitro and in vivo data from Drosophila melanogaster embryos. Throughout prometaphase, puncta of both motors aligned on interpolar microtubules (MTs [ipMTs]), and motor perturbation changed spindle length, as predicted. Competitive motility of purified kinesin-5 and -14 was well described by a stochastic, opposing power stroke model incorporating motor kinetics and load-dependent detachment. Motor parameters from this model were applied to a new stochastic force-balance model for prometaphase spindles, providing a good fit to data from embryos. Maintenance of virtual spindles required dynamic ipMTs and a narrow range of kinesin-5 to kinesin-14 ratios matching that found in embryos. Functional perturbation and modeling suggest that this range can be extended significantly by a disassembling lamin-B envelope that surrounds the prometaphase spindle and augments the finely tuned, antagonistic kinesin force balance to maintain robust prometaphase spindles as MTs assemble and chromosomes are pushed to the equator

Scholey, Jonathan M

eScholarship - University of California

Prometaphase spindle maintenance by an antagonistic motor-dependent force balance made robust by a disassembling lamin-B envelope

A homotetrameric kinesin-5, KLP61F, bundles microtubules and antagonizes Ncd in motility assays.

A role for nuclear lamins in nuclear envelope

Chromosome congression by Kinesin-5 motor-mediated disassembly of longer kinetochore microtubules.

Chromosome motion during attachment to the vertebrate spindle: initial saltatory-like behavior of chromosomes and quantitative analysis of force production by nascent kinetochore fibers.

Computer simulations reveal motor properties generating stable antiparallel microtubule interactions.

Dynamics of the nuclear envelope and of nuclear pore complexes during mitosis in the Drosophila embryo.

Efficient chromosome capture requires a bias in the ‘search-and-capture’ process during mitotic-spindle assembly.

Force production by single kinesin motors.

Genetic analysis of the mitotic spindle.

Individual dimers of the mitotic kinesin motor Eg5 step processively and support substantial loads in vitro.

Kinesin-related proteins required for structural integrity of the mitotic spindle.

Microinjection techniques for studying mitosis in the Drosophila melanogaster syncytial embryo.

Microtubule motors in mitosis.

Mitotic spindle assembly and chromosome segregation: refocusing on microtubule dynamics.

Model for anaphase B: role of three mitotic motors in a switch from poleward flux to spindle elongation.

Model of chromosome motility in Drosophila embryos: adaptation of a general mechanism for rapid mitosis.

Ncd motor binding and transport in the spindle.

Novel roles for Saccharomyces cerevisiae mitotic spindle motors.

Opposing motor activities are required for the organization of the mammalian mitotic spindle pole.

Phosphorylation by Cdk1 increases the binding of Eg5 to microtubules in vitro and in Xenopus egg extract spindles. PLoS One.

Quantitative analysis of an anaphase B switch: predicted role for a microtubule catastrophe gradient.

Reverse engineering of force integration during mitosis in the Drosophila embryo.

The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber.

Two Saccharomyces cerevisiae kinesin-related gene products required for mitotic spindle assembly.

https://escholarship.org/content/qt5qt3d865/qt5qt3d865.pdf?t=qaedqn

Prometaphase spindle maintenance by an antagonistic motor-dependent force balance made robust by a disassembling lamin-B envelope

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eScholarship - University of California