Multiple mechanisms of chromosome movement in vertebrate cells mediated through the Ndc80 complex and dynein/dynactin

V. V. Vorozhko, M. J. Emanuele, Marko Kallio, Gary Gorbsky (Corresponding Author), P. Todd Stukenberg

Research output: Contribution to journalArticleScientificpeer-review

46 Citations (Scopus)

Abstract

Kinetochores bind microtubules laterally in a transient fashion and stably, by insertion of plus ends. These pathways may exist to carry out distinct tasks during different stages of mitosis and likely depend on distinct molecular mechanisms. On isolated chromosomes, we found microtubule nucleation/binding depended additively on both dynein/dynactin and on the Ndc80/Hec1 complex. Studying chromosome movement in living Xenopus cells within the simplified geometry of monopolar spindles, we quantified the relative contributions of dynein/dynactin and the Ndc80/Hec1 complex. Inhibition of dynein/dynactin alone had minor effects but did suppress transient, rapid, poleward movements. In contrast, inhibition of the Ndc80 complex blocked normal end-on attachments of microtubules to kinetochores resulting in persistent rapid poleward movements that required dynein/dynactin. In normal cells with bipolar spindles, dynein/dynactin activity on its own allowed attachment and rapid movement of chromosomes on prometaphase spindles but failed to support metaphase alignment and chromatid movement in anaphase. Thus, in prometaphase, dynein/dynactin likely mediates early transient, lateral interactions of kinetochores and microtubules. However, mature attachment via the Ndc80 complex is essential for metaphase alignment and anaphase A.
Original languageEnglish
Pages (from-to)169-179
JournalChromosoma
Volume117
Issue number2
DOIs
Publication statusPublished - 2008
MoE publication typeA1 Journal article-refereed

Fingerprint

Dyneins
Vertebrates
Chromosomes
Kinetochores
Microtubules
Prometaphase
Anaphase
Metaphase
Chromatids
Xenopus
Mitosis
Dynactin Complex

Keywords

  • chromosomes
  • chromosome movement
  • microtubules
  • dynein
  • dynactin

Cite this

Vorozhko, V. V. ; Emanuele, M. J. ; Kallio, Marko ; Gorbsky, Gary ; Stukenberg, P. Todd. / Multiple mechanisms of chromosome movement in vertebrate cells mediated through the Ndc80 complex and dynein/dynactin. In: Chromosoma. 2008 ; Vol. 117, No. 2. pp. 169-179.
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Multiple mechanisms of chromosome movement in vertebrate cells mediated through the Ndc80 complex and dynein/dynactin. / Vorozhko, V. V.; Emanuele, M. J.; Kallio, Marko; Gorbsky, Gary (Corresponding Author); Stukenberg, P. Todd.

In: Chromosoma, Vol. 117, No. 2, 2008, p. 169-179.

Research output: Contribution to journalArticleScientificpeer-review

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AU - Stukenberg, P. Todd

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AB - Kinetochores bind microtubules laterally in a transient fashion and stably, by insertion of plus ends. These pathways may exist to carry out distinct tasks during different stages of mitosis and likely depend on distinct molecular mechanisms. On isolated chromosomes, we found microtubule nucleation/binding depended additively on both dynein/dynactin and on the Ndc80/Hec1 complex. Studying chromosome movement in living Xenopus cells within the simplified geometry of monopolar spindles, we quantified the relative contributions of dynein/dynactin and the Ndc80/Hec1 complex. Inhibition of dynein/dynactin alone had minor effects but did suppress transient, rapid, poleward movements. In contrast, inhibition of the Ndc80 complex blocked normal end-on attachments of microtubules to kinetochores resulting in persistent rapid poleward movements that required dynein/dynactin. In normal cells with bipolar spindles, dynein/dynactin activity on its own allowed attachment and rapid movement of chromosomes on prometaphase spindles but failed to support metaphase alignment and chromatid movement in anaphase. Thus, in prometaphase, dynein/dynactin likely mediates early transient, lateral interactions of kinetochores and microtubules. However, mature attachment via the Ndc80 complex is essential for metaphase alignment and anaphase A.

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