• Published by: Denis CHRETIEN
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Factors involved in the regulation of microtubule dynamic instability

Dynamic instability is finely regulated in vivo by several proteins, and allows rapid spatial changes of the microtubule cytoskeleton during the cell cycle. One striking example is the complete reorganisation of the interphasic array of microtubules into a bipolar spindle at the onset of mitosis. +TIPs (« plus-end tracking proteins ») interact specifically with the "plus end" of growing microtubules where they regulate microtubule dynamics and their anchoring to multiple subcellular structures (vesicles, kinetochores, cellular cortex). Therefore, +TIPs are involved in essential processes such as spindle formation and orientation, chromosome segregation, and cell migration.

The mechanisms through which +TIPs localize at microtubule plus ends remain unclear, and different models have been proposed: copolymerization with tubulin dimers, recognition of a specific structure at microtubule ends, or transportation by motor proteins. Furthermore, essential questions are still open concerning the specific activity of +TIPs.

Our objectives are to understand how +TIPs interact at microtubule plus ends, and how these proteins regulate microtubule dynamics and their binding to subcellular targets. For these purposes, we are developing cell-free systems using purified components (+TIPs, tubulin, microtubule nucleating-centres). At the experimental level, we use optical video-microscopy and electron cryomicroscopy to associate structural events to particular dynamic behaviors. Two aspects are thus studied: (1) the effects of different +TIPs on microtubule dynamics and structure, and (2) the characterization of microtubule capture by +TIPs. We are currently interested in the following +TIPs:

  1. CLIP-170 (Cytoplasmic Linker Protein), a partner of the cytoplasmic dynein,
  2. EB1 (End-Binding 1), a partner of the APC (Adenomatous Polyposis Coli) tumour suppressor,
  3. XMAP215 (Xenopus Microtubule Associated Protein), a Xenopus protein involved in spindle formation.

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

  • Ensconsin/Map7 promotes microtubule growth and centrosome separation in Drosophila neural stem cells
    Gallaud E., Caous R., Pascal A., Bazile F., Gagné J-P., Huet S., Poirier G. G., Chrétien D., Richard-Parpaillon L., and R. Giet
    The Journal of Cell Biology, 2014, 204:1111-1121.
    Weblink

  • EB1 regulates microtubule dynamics and tubulin sheet closure in vitro
    Vitre, B., Coquelle, F. M., Heichette, C., Garnier, C., Chrétien, D. and I. Arnal
    Nature Cell Biology, 2008, 10:415-421.
    Pubmed