Phosphorylation regulates targeting of cytoplasmic dynein to kinetochores during mitosis

Jacqueline Whyte, Jason R. Bader, Sinji B.F. Tauhata, Maurice Raycroft, Jessica Hornick, K. Kevin Pfister, William S. Lane, Gordon K. Chan, Edward H. Hinchcliffe, Patricia S. Vaughan, Kevin T. Vaughan

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Abstract

Cytoplasmic dynein functions at several sites during mitosis; however, the basis of targeting to each site remains unclear. Tandem mass spec-trometry analysis of mitotic dynein revealed a phosphorylation site in the dynein intermediate chains (ICs) that mediates binding to kinetochores. IC phosphorylation directs binding to zw 10 rather than dynactin, and this interaction is needed for kinetochore dynein localization. Phosphodynein associates with kinetochores from nuclear envelope breakdown to metaphase, but bioriented microtubule (MT) attachment and chromosome alignment induce IC dephosphorylation. IC dephosphorylation stimulates binding to dynactin and poleward streaming. MT depolymerization, release of kinetochore tension, and a PP1-γ mutant each inhibited IC dephosphorylation, leading to the retention of phosphodynein at kinetochores and reduced poleward streaming. The depletion of kinetochore dynactin by moderate levels of p50(dynamitin) expression disrupted the ability of dynein to remove checkpoint proteins by streaming at metaphase but not other aspects of kinetochore dynein activity. Together, these results suggest a new model for localization of kinetochore dynein and the contribution of kinetochore dynactin.

Original languageEnglish (US)
Pages (from-to)819-834
Number of pages16
JournalJournal of Cell Biology
Volume183
Issue number5
DOIs
StatePublished - Dec 1 2008

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    Whyte, J., Bader, J. R., Tauhata, S. B. F., Raycroft, M., Hornick, J., Pfister, K. K., Lane, W. S., Chan, G. K., Hinchcliffe, E. H., Vaughan, P. S., & Vaughan, K. T. (2008). Phosphorylation regulates targeting of cytoplasmic dynein to kinetochores during mitosis. Journal of Cell Biology, 183(5), 819-834. https://doi.org/10.1083/jcb.200804114