Clustering creates a spindle

Individual lobbyists might have a hard time promoting their cause, but get a large group of like-minded individuals together, and there's action. Similarly, the spindle assembly action of Aurora B starts only once this kinase comes together with other chromosomal passenger complex (CPC) members, according to a new study by Alexander Kelly, Hironori Funabiki, and colleagues (Rockefeller University, New York, NY).

Spindle assembly at the chromosomes is controlled by the Aurora B kinase, which deactivates microtubule-destructing proteins MCAK and Op18. The CPC member Dasra A is required for the rest of the CPC to assemble on chromosomes. Kelly et al. now show that this chromosomal loading serves to cluster the CPC components. It is this clustering that then kicks off the Aurora B pathway.

The team induced clustering of the CPC proteins in cell extracts devoid of chromatin using antibodies to a CPC component. This clustering was sufficient to phosphorylate downstream targets of Aurora B and to generate spindles lacking chromosomes.

Clustering, the team showed, allowed the CPC components to effectively phosphorylate each other and ultimately activate Aurora B. They suggest that cytoplasmic phosphatases would dampen the activity of Aurora B that is not bound to chromosomes. Thus, clustering of CPC components by loading onto chromatin provides a “very simple mechanism to spatially control the kinase activity,” says Funabiki.

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