Ran’s downhill slide during mitosis

Hasegawa et al. clarify the role of RanGTP in the formation of the mitotic spindle.

Because RanGTP is prevalent in the cell, its job during spindle assembly has been difficult to nail down. One possibility is that RanGTP promotes construction of the spindle by liberating spindle assembly factors from the importins that carry them. Previous studies of Xenopus egg extracts and fast-dividing cells have discovered a precipitous RanGTP gradient surrounding mitotic chromosomes, which might ensure that the protein triggers the spindle to coalesce near the chromosomes. However, researchers weren’t sure if other, slower-growing cell types showed this steep dropoff in RanGTP levels.

To find out, Hasegawa et al. measured RanGTP gradients in an assortment of mitotic cells. Whereas some cell types, such as highly proliferative HeLa cells, showed steep gradients, other cell types had shallower gradients, and slow-growing HFF-1 fibroblasts exhibited no gradient at all.

The team then altered the slope of the RanGTP gradient in different cells. HeLa cells with a shallower-than-normal gradient spent more time in prometaphase, the stage when spindle microtubules transport the chromosomes to the cell center. This suggests that a steep RanGTP gradient helps orchestrate assembly of a working spindle during prometaphase. The researchers also found that they could make the gradient steeper by fusing HFF-1 cells, forcing them to carry extra chromosomes, which might help explain why aneuploid cancer cells divide more rapidly.