AI Article Synopsis
- Cytoplasmic dynein plays various roles during mitosis, but how it is targeted to different sites is not fully understood.
- Recent analysis identified a phosphorylation site in dynein's intermediate chains that is crucial for binding to kinetochores, which are essential for proper chromosome movement.
- The study reveals that phosphorylation directs dynein to kinetochores during early mitosis, while dephosphorylation later promotes a switch to binding dynactin, facilitating movement toward the poles of the cell.
Article Abstract
Cytoplasmic dynein functions at several sites during mitosis; however, the basis of targeting to each site remains unclear. Tandem mass spectrometry analysis of mitotic dynein revealed a phosphorylation site in the dynein intermediate chains (ICs) that mediates binding to kinetochores. IC phosphorylation directs binding to zw10 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-gamma 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2592828 | PMC |
| http://dx.doi.org/10.1083/jcb.200804114 | DOI Listing |
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