Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 106, Issue 36, Pages 15338-15343Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0902317106
Keywords
stathmin; bipolarity; flux; kinesin-5
Categories
Funding
- National Institutes of Health (NIH) [R01 GM065933, U01 GM067230]
- NIH National Research Service Award [GM078852]
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Accuracy in chromosome segregation depends on the assembly of a bipolar spindle. Unlike mitotic spindles, which have roughly equal amounts of kinetochore microtubules (kMTs) and nonkinetochore microtubules (non-kMTs), vertebrate meiotic spindles are predominantly comprised of non-kMTs, a large subset of which forms an antiparallel barrel'' array at the spindle equator. Though kMTs are needed to drive chromosome segregation, the contributions of non-kMTs are more mysterious. Here, we show that increasing the concentration of Op18/stathmin, a component of the chromosome-mediated microtubule formation pathway that directly controls microtubule dynamics, can be used to deplete non-kMTs in the vertebrate meiotic spindle assembled in Xenopus egg extracts. Under these conditions, kMTs and the spindle pole-associated non-kMT arrays persist in smaller spindles. In excess Op18, distances between sister kinetochores, an indicator of tension across centromeres, remain unchanged, even though kMTs flux poleward with a approximate to 30% slower velocity, and chromosomes oscillate more than in control metaphase spindles. Remarkably, kinesin-5, a conserved motor protein that can push microtubules apart and is required for the assembly and maintenance of bipolar meiotic spindles, is not needed to maintain spindle bipolarity in the presence of excess Op18. Our data suggest that non-kMTs in meiotic spindles contribute to normal kMT dynamics, stable chromosome positioning, and the establishment of proper spindle size. We propose that without non-kMTs, metaphase meiotic spindles are similar to mammalian mitotic spindles, which balance forces to maintain metaphase spindle organization in the absence of extensive antiparallel microtubule overlap at the spindle equator or a key mitotic kinesin.
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