Aurora B suppresses microtubule dynamics and limits central spindle size by locally activating KIF4A.
Anaphase central spindle formation is controlled by the microtubule-stabilizing factor PRC1 and the kinesin KIF4A. We show that an MKlp2-dependent pool of Aurora B at the central spindle, rather than global Aurora B activity, regulates KIF4A accumulation at the central spindle. KIF4A phosphorylation by Aurora B stimulates the maximal microtubule-dependent ATPase activity of KIF4A and promotes its interaction with PRC1. In the presence of phosphorylated KIF4A, microtubules grew more slowly and showed long pauses in growth, resulting in the generation of shorter PRC1-stabilized microtubule overlaps in vitro. Cells expressing only mutant forms of KIF4A lacking the Aurora B phosphorylation site overextended the anaphase central spindle, demonstrating that this regulation is crucial for microtubule length control in vivo. Aurora B therefore ensures that suppression of microtubule dynamic instability by KIF4A is restricted to a specific subset of microtubules and thereby contributes to central spindle size control in anaphase.
Department of Biochemistry, University of Oxford, Oxford OX1 3QU, England, UK.
Ricardo
R
Nunes Bastos
Sapan R
SR
Gandhi
Ryan D
RD
Baron
Ulrike
U
Gruneberg
Erich A
EA
Nigg
Francis A
FA
Barr
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism*; D018411:Spodoptera
C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; C484228:KIF4A protein, human; D016547:Kinesins