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Chromosomal attachments set length and microtubule number in the Saccharomyces cerevisiae mitotic spindle.

Nannas NJ, O'Toole ET, Winey M, Murray AW - Mol. Biol. Cell (2014)

Bottom Line: The length of the mitotic spindle varies among different cell types.A simple model for spindle length regulation requires balancing two forces: pulling, due to micro-tubules that attach to the chromosomes at their kinetochores, and pushing, due to interactions between microtubules that emanate from opposite spindle poles.In the budding yeast Saccharomyces cerevisiae, we show that spindle length scales with kinetochore number, increasing when kinetochores are inactivated and shortening on addition of synthetic or natural kinetochores, showing that kinetochore-microtubule interactions generate an inward force to balance forces that elongate the spindle.

View Article: PubMed Central - PubMed

Affiliation: Molecular and Cellular Biology Department, Harvard University, Cambridge, MA 02138 FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138.

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(A) Spindle components and forces. The kinetochores of sister chromatids attach to microtubules emanating from opposite spindle pole bodies (biorientation) generating inward force (green arrows). Interpolar microtubules interact with the plus-end motor proteins Cin8 and Kip1, generating outward force (red arrows). (B) Force balance model. If the spindle is too short, outward force exceeds inward force, and the spindle elongates, reducing the outward force. The opposite happens if the spindle is too long. (C, D) Force balance predictions. (C) If kinetochores are inhibited (red dots) or cohesion is removed, the spindle will elongate. (D) Spindle length scales with the number of chromosomal attachments. Each attachment contributes inward force; increasing attachment number will shorten spindles, and reducing it will elongate spindles.
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Figure 1: (A) Spindle components and forces. The kinetochores of sister chromatids attach to microtubules emanating from opposite spindle pole bodies (biorientation) generating inward force (green arrows). Interpolar microtubules interact with the plus-end motor proteins Cin8 and Kip1, generating outward force (red arrows). (B) Force balance model. If the spindle is too short, outward force exceeds inward force, and the spindle elongates, reducing the outward force. The opposite happens if the spindle is too long. (C, D) Force balance predictions. (C) If kinetochores are inhibited (red dots) or cohesion is removed, the spindle will elongate. (D) Spindle length scales with the number of chromosomal attachments. Each attachment contributes inward force; increasing attachment number will shorten spindles, and reducing it will elongate spindles.

Mentions: Cells must regulate the size of their internal structures. Some, such as viral capsids, are determined by specific molecular interactions. In others, such as the muscle sarcomere, molecular rulers set the length. The mitotic spindle is a dynamic structure whose size exceeds that of any of its individual components, and its length is set by rules that govern its self-assembly. The spindle is a bipolar array of microtubules that segregates chromosomes (Bloom and Joglekar, 2010). Microtubules attach to chromosomes through kinetochores—protein complexes assembled on centromeric DNA (Westermann et al., 2007). In metaphase, bioriented sister chromatids attach to microtubules from opposite poles and are held together by cohesin rings (Figure 1A). Anaphase chromosome segregation occurs when cohesin is cleaved and sister chromatids are pulled to opposite poles (Tanaka, 2008). Spindle lengths vary from 2 μm in budding yeast (Winey et al., 1995; Straight et al., 1997) to 60 μm in single-celled Xenopus embryos (Wühr et al., 2008), but the spindle of each cell type has a characteristic length (Goshima and Scholey, 2010).


Chromosomal attachments set length and microtubule number in the Saccharomyces cerevisiae mitotic spindle.

Nannas NJ, O'Toole ET, Winey M, Murray AW - Mol. Biol. Cell (2014)

(A) Spindle components and forces. The kinetochores of sister chromatids attach to microtubules emanating from opposite spindle pole bodies (biorientation) generating inward force (green arrows). Interpolar microtubules interact with the plus-end motor proteins Cin8 and Kip1, generating outward force (red arrows). (B) Force balance model. If the spindle is too short, outward force exceeds inward force, and the spindle elongates, reducing the outward force. The opposite happens if the spindle is too long. (C, D) Force balance predictions. (C) If kinetochores are inhibited (red dots) or cohesion is removed, the spindle will elongate. (D) Spindle length scales with the number of chromosomal attachments. Each attachment contributes inward force; increasing attachment number will shorten spindles, and reducing it will elongate spindles.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 1: (A) Spindle components and forces. The kinetochores of sister chromatids attach to microtubules emanating from opposite spindle pole bodies (biorientation) generating inward force (green arrows). Interpolar microtubules interact with the plus-end motor proteins Cin8 and Kip1, generating outward force (red arrows). (B) Force balance model. If the spindle is too short, outward force exceeds inward force, and the spindle elongates, reducing the outward force. The opposite happens if the spindle is too long. (C, D) Force balance predictions. (C) If kinetochores are inhibited (red dots) or cohesion is removed, the spindle will elongate. (D) Spindle length scales with the number of chromosomal attachments. Each attachment contributes inward force; increasing attachment number will shorten spindles, and reducing it will elongate spindles.
Mentions: Cells must regulate the size of their internal structures. Some, such as viral capsids, are determined by specific molecular interactions. In others, such as the muscle sarcomere, molecular rulers set the length. The mitotic spindle is a dynamic structure whose size exceeds that of any of its individual components, and its length is set by rules that govern its self-assembly. The spindle is a bipolar array of microtubules that segregates chromosomes (Bloom and Joglekar, 2010). Microtubules attach to chromosomes through kinetochores—protein complexes assembled on centromeric DNA (Westermann et al., 2007). In metaphase, bioriented sister chromatids attach to microtubules from opposite poles and are held together by cohesin rings (Figure 1A). Anaphase chromosome segregation occurs when cohesin is cleaved and sister chromatids are pulled to opposite poles (Tanaka, 2008). Spindle lengths vary from 2 μm in budding yeast (Winey et al., 1995; Straight et al., 1997) to 60 μm in single-celled Xenopus embryos (Wühr et al., 2008), but the spindle of each cell type has a characteristic length (Goshima and Scholey, 2010).

Bottom Line: The length of the mitotic spindle varies among different cell types.A simple model for spindle length regulation requires balancing two forces: pulling, due to micro-tubules that attach to the chromosomes at their kinetochores, and pushing, due to interactions between microtubules that emanate from opposite spindle poles.In the budding yeast Saccharomyces cerevisiae, we show that spindle length scales with kinetochore number, increasing when kinetochores are inactivated and shortening on addition of synthetic or natural kinetochores, showing that kinetochore-microtubule interactions generate an inward force to balance forces that elongate the spindle.

View Article: PubMed Central - PubMed

Affiliation: Molecular and Cellular Biology Department, Harvard University, Cambridge, MA 02138 FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138.

Show MeSH