Spindle maintenance machinery identified

During cell division, microtubules emanating from each of the spindle poles meet and overlap in the spindle’s mid zone. Now, scientists have uncovered the molecular mechanism that determines the extent of this overlap.

In a study published in Cell, scientists were able to reconstruct such anti-parallel microtubule overlaps in vitro and identify two proteins that are sufficient to control the formation and size of this important spindle feature.

Thomas Surrey and his group at the European Molecular Biology Laboratory in Heidelberg, Germany, found that one protein – PRC1 – bundles together microtubules coming from opposite ends of the cell, attaching them to each other. It then recruits a second protein, a molecular motor from the kinesin-4 subfamily, increasing its concentration in the spindle mid zone.

This motor walks along the overlapping microtubules like an officer on patrol, until it reaches one of the ends. When enough kinesin-4 molecules reach the end of the overlap, they inhibit the growth of microtubules there, keeping the overlap size constant without affecting microtubules elsewhere in the cell.

The spindle mid zone plays an important part not only in helping to align the chromosomes in metaphase but also in the final stages of cell division, when it drives the physical separation of the two daughter cells. But between these two stages, the two ends of the spindle must move away from each other, to drag half the genetic material to each side of the dividing cell.

At this point, if PRC1 and kinesin-4 had stopped microtubule growth permanently in the central part of the spindle, the overlap would become smaller and smaller until the spindle itself collapsed, jeopardising cell division; however, Surrey and colleagues found that PRC1 and kinesin-4 control the overlap size in an adaptive manner.

As the spindle stretches and the overlap between microtubules becomes smaller, the scientists posit, the inhibitory effect of kinesin-4 diminishes, allowing the microtubule ends to grow.

‘Our findings show how molecules millionths of millimetres small can control the size of a structure about a thousand times larger than themselves,’ stated Surrey, before concluding: ‘They help us to understand the fundamentals of cell division.’

Further reading

Bieling, P. et al. (2010) A minimal midzone protein module controls formation and length of antiparallel microtubule overlaps. Cell 142, 335–496

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