A new mechanism controlling kinetochore-microtubule interactions revealed by comparison of two dynein-targeting components: SPDL-1 and the Rod/Zwilch/Zw10 complex

Reto Gassmann, Anthony Essex, Jia Sheng Hu, Paul S. Maddox, Fumio Motegi, Asako Sugimoto, Sean M. O'Rourke, Bruce Bowerman, Ian McLeod, John R. Yates, Karen Oegema, Iain M. Cheeseman, Arshad Desai

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Chromosome segregation requires stable bipolar attachments of spindle microtubules to kinetochores. The dynein/dynactin motor complex localizes transiently to kinetochores and is implicated in chromosome segregation, but its role remains poorly understood. Here, we use the Caenorhabditis elegans embryo to investigate the function of kinetochore dynein by analyzing the Rod/Zwilch/Zw10 (RZZ) complex and the associated coiled-coil protein SPDL-1. Both components are essential for Mad2 targeting to kinetochores and spindle checkpoint activation. RZZ complex inhibition, which abolishes both SPDL-1 and dynein/dynactin targeting to kinetochores, slows but does not prevent the formation of load-bearing kinetochore-microtubule attachments and reduces the fidelity of chromosome segregation. Surprisingly, inhibition of SPDL-1, which abolishes dynein/dynactin targeting to kinetochores without perturbing RZZ complex localization, prevents the formation of load-bearing attachments during most of prometaphase and results in extensive chromosome missegregation. Coinhibition of SPDL-1 along with the RZZ complex reduces the phenotypic severity to that observed following RZZ complex inhibition alone. We propose that the RZZ complex can inhibit the formation of load-bearing attachments and that this activity of the RZZ complex is normally controlled by dynein/dynactin localized via SPDL-1. This mechanism could coordinate the hand-off from initial weak dynein-mediated lateral attachments, which help orient kinetochores and enhance their ability to capture microtubules, to strong end-coupled attachments that drive chromosome segregation.

Original languageEnglish
Pages (from-to)2385-2399
Number of pages15
JournalGenes and Development
Volume22
Issue number17
DOIs
Publication statusPublished - 2008 Sep 2
Externally publishedYes

Keywords

  • Aneuploidy
  • Centromere
  • Chromosome
  • Kinetochore
  • Microtubule
  • Mitosis
  • Spindle

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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  • Cite this

    Gassmann, R., Essex, A., Hu, J. S., Maddox, P. S., Motegi, F., Sugimoto, A., O'Rourke, S. M., Bowerman, B., McLeod, I., Yates, J. R., Oegema, K., Cheeseman, I. M., & Desai, A. (2008). A new mechanism controlling kinetochore-microtubule interactions revealed by comparison of two dynein-targeting components: SPDL-1 and the Rod/Zwilch/Zw10 complex. Genes and Development, 22(17), 2385-2399. https://doi.org/10.1101/gad.1687508