• Published by: Denis CHRETIEN
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Molecular basis of microtubule dynamic instability

Microtubules display a unique dynamic behavior for a polymer, since they can alternate autonomously between growth and shrinkage states. This particular behavior, called “dynamic instability”, allows microtubules to explore the intracellular space or to reorganize rapidly to build complex structures such as the mitotic spindle.

The molecular bases of microtubule dynamic instability remain enigmatic. Nevertheless, some points seem to be well established: during assembly, tubulin hydrolyses one molecule of guanosine triphosphate (GTP) into guanosine diphosphate (GDP). The energy associated to this reaction is not released during assembly, but remains stored as mechanical energy that tends to destabilize the microtubule wall. Thus, in order to grow, microtubules must be protected at their extremity by a particular structure. Loss of this structure would induce fast depolymerization events (known as “catastrophes”), while regain of this structure during disassembly would allow the reverse events (“rescues”).

Our works on the mechanisms of microtubule assembly allowed us to propose that their dynamic instability has a strong mechanical component. The special conformation of the tubulin molecules in the growing sheets would protect the unstable microtubule lattice from depolymerization, while closure of these sheets onto energetically unfavorable configurations would account for catastrophes. We pursue our studies with the aim to test these hypotheses, and study diverses factors (proteins, pharmaceutical molecules) that interfere with or regulate microtubule dynamic instability in cells.

Selected publications

  • EB1 interacts with outwardly curved and straight regions of the microtubule lattice
    Guesdon A., Bazile F., Buey R.M., Mohan R., Monier S., Rodríguez García R., Angevin M., Heichette C., Wieneke R., Tampé R., Duchesne L., Akhmanova A., Steinmetz M.O., and D. Chrétien
    Nature Cell Biology, 2016, Sept 12
    Pubmed - Springer Nature Sharing

  • Mechanical stress induced mechanism of microtubule catastrophes
    Hunyadi, V., Chrétien, D. and I. M. Jánosi
    Journal of Molecular Biology, 2005, 348:927-938
    PubMed

  • Microtubule's conformational cap
    Chrétien, D., Jánosi, I., Taveau, J. C. and H. Flyvbjerg
    Cell Structure and Function, 1999, 24:299-303
    PubMed html PDF (910 Ko)