Spindle assembly in the absence of a RanGTP gradient requires localized CPC activity
Open accessAbstract
During animal cell division, a gradient of GTP-bound Ran is generated around mitotic chromatin. It is generally accepted that this RanGTP gradient is essential for organizing the spindle, because it locally activates critical spindle assembly factors. Here, we show in Xenopus laevis egg extract, where the gradient is best characterized, that spindles can assemble in the absence of a RanGTP gradient. Gradient-free spindle assembly occurred around sperm nuclei but not around chromatin-coated beads and required the chromosomal passenger complex (CPC). Artificial enrichment of CPC activity within hybrid bead arrays containing both immobilized chromatin and the CPC supported local microtubule assembly even in the absence of a RanGTP gradient. We conclude that RanGTP and the CPC constitute the two major molecular signals that spatially promote microtubule polymerization around chromatin. Furthermore, we hypothesize that the two signals mainly originate from discreet physical sites on the chromosomes to localize microtubule assembly around chromatin: a RanGTP signal from any chromatin and a CPC-dependent signal predominantly generated from centromeric chromatin.
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The local concentrations and activation of Ran-GTP and Aurora B/CPC could differentially affect the activity of their downstream targets, some of which are identical between the two pathways.
“While it is known that both pathways contribute to spindle assembly [60], their local concentrations and activation could differentially affect the activity of their downstream targets, some of which are identical between the two pathways.”
From Regulatory mechanisms that control mitotic kinesins (2015) · cites this paper as [60]
Both the Ran-GTP and Aurora B/CPC pathways contribute to spindle assembly.
“While it is known that both pathways contribute to spindle assembly [60], their local concentrations and activation could differentially affect the activity of their downstream targets, some of which are identical between the two pathways.”
From Regulatory mechanisms that control mitotic kinesins (2015) · cites this paper as [60]
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“While it is known that both pathways contribute to spindle assembly [60], their local concentrations and activation could Yount et al.”
Background
- Authors
- Maresca, T. J., Groen, A. C., Gatlin, J. C., Ohi, R., Mitchison, T. J., & Salmon, E. D.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Marine Biological Laboratory (US)
- Vanderbilt University Medical Center (US)
- Corresponding author
- Maresca, Thomas J.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 19
- Issue
- 14
- Pages
- 1210-1215
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC2752711
- OpenAlex
- W2121696619
- Cited by
- 89
- References
- 27
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 8 · 2020: 4 · 2019: 8 · 2018: 3 · 2017: 3 · 2016: 7 · 2015: 11 · 2014: 3 · 2013: 6 · 2012: 5
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- Open Access Server of the Woods Hole Scientific Community (Woods Hole Scientific Community) (submittedVersion)
- UNC Libraries
- Funders
- National Institutes of Health (GM-24364)
- National Cancer Institute (CA078048-09, P01CA078048, CA078048)
- National Institute of General Medical Sciences (R37GM024364, GM24364, F32GM080049, R01GM024364)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- spindle assembly, chromosomal passenger complex, microtubule nucleation, mitosis, centromeric chromatin, sperm nucleus, Xenopus egg extracts, mitotic chromatin, microtubule assembly
- MeSH terms
- Animals, Cell Division, Chromatin, Kinetics, Microscopy, Fluorescence, Microspheres, Microtubules, Spindle Apparatus, Xenopus laevis, Protein Serine-Threonine Kinases, Centrosome, Kinetochores, ran GTP-Binding Protein, Multiprotein Complexes, Aurora Kinases
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