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Published online June 18, 2007
doi:10.1083/jcb.200702062
The Journal of Cell Biology, Vol. 177, No. 6, 1005-1015
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Griffis et al.
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Article

 Spindly, a novel protein essential for silencing the spindle assembly checkpoint, recruits dynein to the kinetochore

Eric R. Griffis1,2, Nico Stuurman1,2, and Ronald D. Vale1,2

1 Howard Hughes Medical Institute and 2 Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158

Correspondence to Ronald D. Vale: vale{at}cmp.ucsf.edu

The eukaryotic spindle assembly checkpoint (SAC) monitors microtubule attachment to kinetochores and prevents anaphase onset until all kinetochores are aligned on the metaphase plate. In higher eukaryotes, cytoplasmic dynein is involved in silencing the SAC by removing the checkpoint proteins Mad2 and the Rod–Zw10–Zwilch complex (RZZ) from aligned kinetochores (Howell, B.J., B.F. McEwen, J.C. Canman, D.B. Hoffman, E.M. Farrar, C.L. Rieder, and E.D. Salmon. 2001. J. Cell Biol. 155:1159–1172; Wojcik, E., R. Basto, M. Serr, F. Scaerou, R. Karess, and T. Hays. 2001. Nat. Cell Biol. 3:1001–1007). Using a high throughput RNA interference screen in Drosophila melanogaster S2 cells, we have identified a new protein (Spindly) that accumulates on unattached kinetochores and is required for silencing the SAC. After the depletion of Spindly, dynein cannot target to kinetochores, and, as a result, cells arrest in metaphase with high levels of kinetochore-bound Mad2 and RZZ. We also identified a human homologue of Spindly that serves a similar function. However, dynein's nonkinetochore functions are unaffected by Spindly depletion. Our findings indicate that Spindly is a novel regulator of mitotic dynein, functioning specifically to target dynein to kinetochores.

Abbreviations used in this paper: APC, anaphase-promoting complex; CENP, centromere protein; Con A, concanavalin A; DHC, dynein heavy chain; DIC, dynein intermediate chain; dsRNA, double-stranded RNA; RZZ, Rod–Zw10–Zwilch complex; SAC, spindle assembly checkpoint; UTR, untranslated region.


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