Phosphorylated kinetochore dynein (red) at late prometaphase.

Whyte et al. now show how dynein gets to and from the kinetochore at mitosis. Their findings also suggest an unexpected role for dynein as a metaphase checkpoint regulator.

The molecular motor, dynein, is important for mitosis and is present at the spindle poles, cell cortex, and kinetochores. How it is targeted to these sites has been something of a mystery.

The authors looked for mitosis-specific post-translational modifications that might affect dynein's targeting. They found a threonine residue in dynein's intermediate chain (T89) that was phosphorylated from the onset of mitosis until metaphase. The authors made an antibody specific for the phospho-T89 form of dynein and showed that it located exclusively to kinetochores.

When the kinetochores were stretched as chromosomes aligned at the metaphase plate, T89 was dephosphorylated by the phosphatase PP1γ. As a result, dynein lost its association with the kinetochore and headed out along metaphase microtubules toward the spindle poles. Fluorescence colocalization studies showed that poleward-streaming dynein took with it metaphase checkpoint proteins like BubR1.

Kinetochore dynein was thought to be involved in the poleward movement of chromosomes during anaphase. But, the stripping away of metaphase checkpoint proteins from the kinetochore might actually be the main role of kinetochore dynein in mitosis, says author Kevin Vaughan.

Whyte, J., et al.
J. Cell Biol.