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Cited by 396Microtubule and mitosis dynamicsGenomics and Chromatin DynamicsCancer Treatment and Pharmacology

A model for the proposed roles of different microtubule-based motor proteins in establishing spindle bipolarity

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Walczak, Claire E., Vernos, Isabelle, Mitchison, Timothy J., Karsenti, Eric, Heald, Rebecca·1998·Current Biology
DOI 10.1016/s0960-9822(07)00370-3
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Abstract

Background In eukaryotes, assembly of the mitotic spindle requires the interaction of chromosomes with microtubules. During this process, several motor proteins that move along microtubules promote formation of a bipolar microtubule array, but the precise mechanism is unclear. In order to examine the roles of different motor proteins in building a bipolar spindle, we have used a simplified system in which spindles assemble around beads coated with plasmid DNA and incubated in extracts from Xenopus eggs. Using this system, we can study spindle assembly in the absence of paired cues, such as centrosomes and kinetochores, whose microtubule-organizing properties might mask the action of motor proteins.Results We blocked the function of individual motor proteins in the Xenopus extracts using specific antibodies. Inhibition of Xenopus kinesin-like protein 1 (Xklp1) led either to the dissociation of chromatin beads from microtubule arrays, or to collapsed microtubule bundles on beads. Inhibition of Eg5 resulted in monopolar microtubule arrays emanating from chromatin beads. Addition of antibodies against dynein inhibited the focusing of microtubule ends into spindle poles in a dose-dependent manner. Inhibition of Xenopus carboxy-terminal kinesin 2 (XCTK2) affected both pole formation and spindle stability. Co-inhibition of XCTK2 and dynein dramatically increased the severity of spindle pole defects. Inhibition of Xklp2 caused only minor spindle pole defects.Conclusions Multiple microtubule-based motor activities are required for the bipolar organization of microtubules around chromatin beads, and we propose a model for the roles of the individual motor proteins in this process.

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  • The second role of minus end-directed kinesins is to organize spindle MTs at MT minus ends and focus them into spindle poles.

    “The second role is to organize spindle MTs at MT minus ends and focus them into spindle poles (5)(6)(7).”

    From Diffusion and Directed Movement (2008) · cites this paper as [6]

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Authors
Walczak, C. E., Vernos, I., Mitchison, T. J., Karsenti, E., & Heald, R.
Affiliations
  • University of California, San Francisco (US)
  • European Molecular Biology Laboratory (DE)
  • Harvard University (US)
  • University of California, Berkeley (US)
Corresponding author
Heald, Rebecca
ORCID
Venue
Current Biology
Publisher
Elsevier BV
Published
1998-07
Volume
8
Issue
16
Pages
903-913
ISSN
0960-9822 (ISSN-L)
DOI
10.1016/s0960-9822(07)00370-3
OpenAlex
W2085102956
Cited by
396
References
59
Citations by year
2026: 1 · 2025: 2 · 2024: 8 · 2023: 10 · 2022: 8 · 2021: 13 · 2020: 9 · 2019: 13 · 2018: 7 · 2017: 9 · 2016: 13 · 2015: 9 · 2014: 10 · 2013: 7 · 2012: 14
FWCI
9.48
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Biology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords
mitotic spindle assembly, spindle bipolarity, microtubule motor proteins, Eg5, dynein, microtubule bundling, Xenopus egg extracts, monopolar spindle
MeSH terms
Animals, Chromatin, Female, Meiosis, Metaphase, Microtubule-Associated Proteins, Microtubules, Spindle Apparatus, Models, Biological, Oocytes, Tissue Extracts, Xenopus laevis, Kinesins, Cell Polarity, Xenopus Proteins

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