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

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.

journal_name

Genes Dev

journal_title

Genes & development

authors

Gassmann R,Essex A,Hu JS,Maddox PS,Motegi F,Sugimoto A,O'Rourke SM,Bowerman B,McLeod I,Yates JR 3rd,Oegema K,Cheeseman IM,Desai A

doi

10.1101/gad.1687508

subject

Has Abstract

pub_date

2008-09-01 00:00:00

pages

2385-99

issue

eissn

0890-9369

issn

1549-5477

pii

22/17/2385

journal_volume

pub_type

杂志文章

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