InterPro domain: IPR009361

Zeste white 10 (ZW10) was initially identified as a mitotic checkpoint protein involved in chromosome segregation, and then implicated in targeting cytoplasmic dynein and dynactin to mitotic kinetochores, but it is also important in non-dividing cells. These include cytoplasmic dynein targeting to Golgi and other membranes, and SNARE-mediated ER-Golgi trafficking [ 1 , 2 ]. Dominant-negative ZW10, anti-ZW10 antibody, and ZW10 RNA interference (RNAi) cause Golgi dispersal. ZW10 RNAi also disperse endosomes and lysosomes [ 3 ].

Drosophila kinetochore components Rough deal (Rod) and Zw10 are required for the proper functioning of the metaphase checkpoint in flies [ 3 ]. The eukaryotic spindle assembly checkpoint (SAC) monitors microtubule attachment to kinetochores and prevents anaphase onset until all kinetochores are aligned on the metaphase plate. It is an essential surveillance mechanism that ensures high fidelity chromosome segregation during mitosis. 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 [ 4 , 5 , 6 ].

1. ZW10 function in mitotic checkpoint control, dynein targeting and membrane trafficking: is dynein the unifying theme? Cell Cycle 5, 2447-51
2. Role of the kinetochore/cell cycle checkpoint protein ZW10 in interphase cytoplasmic dynein function. J. Cell Biol. 172, 655-62
3. Rough deal and Zw10 are required for the metaphase checkpoint in Drosophila. Nat. Cell Biol. 2, 939-43
4. Spindly, a novel protein essential for silencing the spindle assembly checkpoint, recruits dynein to the kinetochore. J. Cell Biol. 177, 1005-15
5. Stable hZW10 kinetochore residency, mediated by hZwint-1 interaction, is essential for the mitotic checkpoint. J. Cell Biol. 180, 507-20
6. Kinetochore dynein is required for chromosome motion and congression independent of the spindle checkpoint. Curr. Biol. 17, 973-80