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Kif18A and Chromokinesins Confine Centromere Movements via Microtubule Growth Suppression and Spatial Control of Kinetochore Tension

2012; Elsevier BV; Volume: 22; Issue: 5 Linguagem: Inglês

10.1016/j.devcel.2012.02.013

1878-1551

Jason Stumpff, Michael Wagenbach, Andrew D. Franck, Charles L. Asbury, Linda Wordeman,

Photosynthetic Processes and Mechanisms

Alignment of chromosomes at the metaphase plate is a signature of cell division in metazoan cells, yet the mechanisms controlling this process remain ambiguous. Here we use a combination of quantitative live-cell imaging and reconstituted dynamic microtubule assays to investigate the molecular control of mitotic centromere movements. We establish that Kif18A (kinesin-8) attenuates centromere movement by directly promoting microtubule pausing in a concentration-dependent manner. This activity provides the dominant mechanism for restricting centromere movement to the spindle midzone. Furthermore, polar ejection forces spatially confine chromosomes via position-dependent regulation of kinetochore tension and centromere switch rates. We demonstrate that polar ejection forces are antagonistically modulated by chromokinesins. These pushing forces depend on Kid (kinesin-10) activity and are antagonized by Kif4A (kinesin-4), which functions to directly suppress microtubule growth. These data support a model in which Kif18A and polar ejection forces synergistically promote centromere alignment via spatial control of kinetochore-microtubule dynamics.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJhNTdiYTc2NTNmYzZiODhhYzdlZWE5Y2NmYjg2NWVjZSIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc3OTYxNDM0fQ.T5-KOOAg68tKzVVy0R5PQQTJXSomIYotw2MQaHDAsA610ZLdsMuSOuJsnJ6gYC-e6AA9wrhlBODombYvCrRk10JLaQlBDViLIRzN4UhvEptXwXSVND5OADIpcPXnUAZz6gNpmvxs4pzJ75sjIAtQl6PfV-L_Gitxes-OaWlwE8_XfwXCA9hA2Iz-DQwW_e2JSwIBCzUmHmJ-oauLrlK9NvuTuj97YvMbrD2DNodQe8gwkgsYxrH5y89m_bmhMnPgqG9eO0qT0Z7KV3xVna6L-KzO0KT8YQG0NFdahC7PwBhRvrVvOD3fhhQyOwD3Ik7a8fbm4ArgXPvIe4Uxg7Y-Aw(mp4, (15.95 MB) Download video