Nunes Bastos et al. describe how the kinesin motor KIF4A restricts its own activity during anaphase by recruiting the phosphatase PP2A-B56 to the central spindle.
During mitosis, KIF4A limits the size of the central spindle by suppressing the growth of microtubules in the spindle midzone. The kinase Aurora B phosphorylates KIF4A to promote the kinesin’s localization and motor activity, but a phosphatase must reverse this modification so that the central spindle can extend and push sister chromatids apart at the later stages of anaphase. The PP2A–B56 phosphatase family opposes Aurora B’s functions in other mitotic processes, so Nunes Bastos et al. examined whether any of the five family members regulated KIF4A.
The researchers found that two PP2A–B56 isoforms, γ and ε, dephosphorylated KIF4A in vitro and localized to the central spindle in anaphase cells. The phosphatases accumulated at the spindle midzone by binding to KIF4A itself, indicating that the kinesin’s localization and activity is restricted by a negative feedback loop. In the absence of B56γ and B56ε, increased amounts of active KIF4A accumulated at the central spindle, which therefore failed to completely extend during anaphase.
Other members of the PP2A–B56 family localize elsewhere in the cell or, in the case of B56β, localize to the central spindle but fail to bind or dephosphorylate KIF4A. Senior author Francis Barr now wants to understand the basis of these different specificities.
Text by Ben Short