Mutations in the Drosophila melanogaster zw10 gene, which encodes a conserved, essential kinetochore component, abolish the ability of dynein to localize to kinetochores. Several similarities between the behavior of ZW10 protein and dynein further support a role for ZW10 in the recruitment of dynein to the kinetochore: (a) in response to bipolar tension across the chromosomes, both proteins mostly leave the kinetochore at metaphase, when their association with the spindle becomes apparent; (b) ZW10 and dynein both bind to functional neocentromeres of structurally acentric minichromosomes; and (c) the localization of both ZW10 and dynein to the kinetochore is abolished in cells mutant for the gene rough deal. ZW10's role in the recruitment of dynein to the kinetochore is likely to be reasonably direct, because dynamitin, the p50 subunit of the dynactin complex, interacts with ZW10 in a yeast two-hybrid screen. Since in zw10 mutants no defects in chromosome behavior are observed before anaphase onset, our results suggest that dynein at the kinetochore is essential for neither microtubule capture nor congression to the metaphase plate. Instead, dynein's role at the kinetochore is more likely to be involved in the coordination of chromosome separation and/or poleward movement at anaphase onset.
ZW10 Helps Recruit Dynactin and Dynein to the Kinetochore
Address all correspondence to Michael L. Goldberg, Section of Genetics and Development, Cornell University, Ithaca, NY 14853-2703. Tel.: (607) 254-4802. Fax: (607) 255-6249. E-mail: [email protected]
We would like to dedicate this paper to the memory of B. Keller (Cornell University, Ithaca, NY). We thank Z. Li and E. Williams (both from Cornell University) for technical help, M. Serr and S. O'Rourke (both from University of Minnesota, St. Paul, MN) for the Dhc antibodies, T. Murphy and G. Karpen (both from The Salk Institute, La Jolla, CA) for the minichromosome stocks, J. Lis and C. Bayles (both from Cornell University) for assistance with CCD microscopy, and F. Scaerou and R. Karess (both from CNRS Centre de Génétique Moléculaire, Gif-sur-Yvette, France) for helpful discussion. We are indebted to C. Echeverri and R. Vallee (both from University of Massachusetts Medical Center, Boston, MA) for insightful discussions and artistic help in preparing Fig. 8.
This research was supported by a grant from the National Institutes of Health (NIH) to M.L. Goldberg (GM 48430) and by an NIH training grant (GM 07617) to the Field of Genetics and Development at Cornell University (Ithaca, NY).
D.A. Starr and B.C. Williams contributed equally to this work.
Daniel A. Starr, Byron C. Williams, Thomas S. Hays, Michael L. Goldberg; ZW10 Helps Recruit Dynactin and Dynein to the Kinetochore . J Cell Biol 10 August 1998; 142 (3): 763–774. doi: https://doi.org/10.1083/jcb.142.3.763
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