Cell ‘skeletons’ help keep cell division on track and cancer in check

04 April 2016

Image sequence of a microtubule in blue with the cap indicated at the end.

Image: Image sequence of a microtubule in blue with the cap indicated at the end. By preventing the formation of new cap sites, we measure how the existing cap sites decay until a critical threshold is reached and the microtubule shrinks (lower two images).

Scientists at the Francis Crick Institute in London have greatly improved our understanding of how microtubules in the cell cytoskeleton switch between phases of growth and shrinkage.

This has implications for cancer research because correct switching frequency between growth and shrinkage is essential for cell division - and cancer can result when cell division goes awry.

Dr Christian Duellberg of the Crick, in Thomas Surrey's lab, explained: "In analogy to the skeleton, cells have a cytoskeleton. Microtubules form part of this cytoskeleton and are little tubes that span throughout the space inside a cell.

"Unlike our static bones, microtubules change their length constantly and switch between phases of growth and shrinkage. This is important because cells need to be able to drastically change their shape when they divide or move. However, exactly how this switching occurs was unknown and has been a controversial topic in the last decades."

Most scientists agree that there has to be some sort of stabilising 'cap' at the end of microtubules. However,

how the size of this cap affects the stability of the microtubules was unknown.

To investigate, the team measured the properties of the cap in space (size) and time (duration of stability). They revealed for the first time a clear link between the cap and microtubule stability - the longer the cap, the more stable the microtubule.

They showed that so-called End Binding (EB) proteins can bind to the cap and make the microtuble unstable, which causes it to switch from growing to shrinking more often. The scientists also showed that these EB proteins, when labelled with dye, can be used to measure the length of the cap by proxy and can therefore be used to track microtubule stability directly and in real time using light microscopy.

Dr Duellberg said: "Because the correct switching frequency between growth and shrinkage of microtubules is essential for cell division, drugs that affect this switching frequency have become powerful tools in chemotherapy as they prevent cells from dividing.

"An example of such a drug is Paclitaxel, which reduces the switching frequency from growth to shrinkage. It is currently used to treat forms of ovarian, breast, lung, pancreatic and other cancers. However, resistance to the drug and side effects are a problem. As our study provides more details into how microtubules switch from growth to shrinkage, this might help to design better drugs that affect microtubule properties more specifically."

As well as offering new insights into cancer, using dye-labelled EB proteins to follow the stability of microtubules in real time will help scientists find out more about diseases

caused by altered microtubule stability and incorrect switching between growth and shrinkage. Examples include eye movement disorders such as strabismus, where a patient's eyes don't align correctly. The paper, The size of the EB cap determines instantaneous microtubule stability, is published in the journal eLife.

  • New insights into how microtubules in the cell cytoskeleton switch between phases of growth and shrinkage have implications for cancer research. Correct switching frequency between growth and shrinkage is essential for cell division - and cancer can result when cell division goes awry.
  • The Francis Crick Institute scientists worked with David Holmes of the London Centre for Nanotechnology. The work was supported by Cancer Research UK, the Francis Crick Institute and the European Research Council.