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Lattice defects induce microtubule self-renewal

Laura Schaedel, Denis Chrétien, Charlotte Aumeier, Jérémie Gaillard, Laurent Blanchoin, Manuel Théry, Karin John

Preprint posted on January 16, 2018 https://www.biorxiv.org/content/early/2018/01/16/249144

Article now published in Nature Physics at http://dx.doi.org/10.1038/s41567-019-0542-4

How do microtubules repair themselves? Recent preprint shows the occurrence of tubulin dimer exchange all along the microtubules at sites of structural defects. After all, defects are a good thing!

Selected by Satish Bodakuntla

 

Context: The well-established microtubule property of dynamic instability allows them to co-exist in both growing and shrinking states. Nevertheless, the site of incorporation of tubulin dimers – laterally, or at the plus ends of microtubules – has long been discussed in the field. Latest studies showed that microtubules subjected to mechanical stress are able to self-repair by incorporating tubulin dimers laterally at the damaged sites.

Key findings: The authors investigate the possibility of spontaneous (in the absence of mechanical stress) microtubule turnover in vitro and provide insights on various factors that could influence this process. They discover the following:

  1. Tubulin incorporation occurs all along the microtubule shafts spontaneously and is dependent on the concentration of free tubulin, similar to what has been found at microtubule plus ends.
  2. Simulations of microtubule dynamics at the dislocation defects (changes in number of protofilaments and/or start number of helices) revealed that small lattice defects are sufficient to trigger tubulin dimer exchange.
  3. Increased free tubulin concentration enhances the microtubule growth rate, which in turn leads to higher lattice-defect frequencies.
  4. Higher lattice-defect frequencies are coupled with increased tubulin incorporation along the microtubule shafts.

Why I am interested in this preprint: Earlier studies from the authors showed that microtubules self-repair in response to mechanical stress, and provided very valuable insights in understanding how long-lived microtubules, such those in axons, tolerate forces they experience. Although there are reports supporting the entry of tubulin dimers along the microtubule shafts, the underlying mechanisms remained unexplored. In this preprint, the authors suggest a possible mechanism: structural defects, in particular, changes in protofilament number along microtubules can trigger the tubulin dimer exchange. Their experiments convincingly support the hypothesis.

In the light of their findings, it prompts us to rethink about the regulation of the microtubule cytoskeleton. Given the incorporation of tubulin dimers along the microtubule lattice, it is possible that this conformation of tubulin can recruit different microtubule-associated proteins thereby inducing dynamic changes in the microtubule properties. I believe the physiological implications of these phenomena will raise new challenging questions in the field.

Questions the work raises:

Microtubules in these experiments are prepared from purified brain tubulin, which is highly enriched with post-translational modifications. I would be curious to know how the results might change if authors had used non-modified tubulin.

 

Tags: dislocation defects, dynamic instability, lattice defects, microtubules

Posted on: 15th February 2018 , updated on: 20th February 2018

Read preprint (4 votes)




Author's response

Manuel Thery shared

The beauty of Laura’s work is that her minimalist approach, in which there is nothing else than tubulin in a very controled fluidic environment, allowed her to reveal a core microtubule property, which had remained hidden for many years behind many other effects that are inherent to more physiological but also more complex conditions.

What she revealed is that microtubules are like us: they permanently self-renew. This observation demonstrates a mechanism that we had hypothesized in our previous study: the possibility to add or remove dimers in the lattice confers to microtubules the ability to self-repair in response to physical injuries. We are amazed by the level of plasticity in these structures! Furthermore, Laura showed, with the help of unpublished 25-year-old cryoEM experiments performed by Denis Chrétien, that renewal happens where tubulins lack one or two neighbours. I am quite excited by the idea that this could not happen in a perfect structure, at least in a reasonable amount of time. Defects make microtubules more sensitive, capable to adapt to external stimulations and probably to live longer.

I found fascinating that this property to undergo permanent self-renewal without apparent changes, which is a characteristic of all living organisms, is so deeply buried in ourselves that it exist even in the filaments our cells are made of.

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