Coordination spatio-temporelle des régulateurs du réseau branché d’actine dans les structures motiles
Soutenue le 13 décembre 2016
Directeur de thèse: Grégory GIANNONE/ Team leader : Spatio-temporal and mechanical control of motile structures / CNRS UMR 5297 – Interdisciplinary Institute for NeuroScience (IINS)
Cell motility is an integrated process involved in critical phenomena such as axonal pathfinding and synaptic plasticity. Dysregulation of cell motility can induce metastasis and abnormal spine shapes observed in neuropsychiatric disorders like autism and schizophrenia. Therefore it is essential to understand how cell motility is regulated. Cell motility requires the formation of branched actin networks propelled by actin polymerization that lead to the formation of membrane protrusions such as the lamellipodium. Several actin regulatory proteins are involved in this process, such as Rac1 and the WAVE and ARP2/3 complexes.
Using single protein tracking, we revealed key phenomena concerning the spatio-temporal regulation of lamellipodium formation by actin regulatory proteins.
We found that the localization and activation of the WAVE complex was enzymatically regulated, but also mechanically. First, we showed that the Rac1 RhoGTPase activates the WAVE complex specifically at the tip of the lamellipodium. We also showed that WAVE complex localization is regulated by the dynamics of branched-network actin filaments.
This study confirms the crucial role of the WAVE complex in lamellipodium formation and reveals the existence of a mechanical regulation of the localization of this complex in the cell.
Keywords: Lamellipode ; Actine ; Complexe Wave ; Complexe Arp2/3 ; Rac1 ; RhoA ; Super-résolution, PALM
Publication: Chazeau A., Mehidi A., Nair D., Gautier J.J., Leduc C., Chamma I., Kage F., Kechkar A., Thoumine O., Rottner K., Choquet D., Gautreau A., Sibarita J., Giannone G. Nanoscale segregation of actin nucleation and elongation factors determines dendritic spine protrusion. 2014 – EMBO J.
- Isabelle SAGOT (Président),
- Laurent BLANCHOIN (rapporteur),
- Stephane BODIN (rapporteur),
- Klemens ROTTNER (Examinateur),
- Violaine MOREAU (Examinateur)
- Olivier ROSSIER (Invité)
- Grégory GIANNONE Directeur de thèse
Chargé de recherche – PhD
CNRS. Institut Interdisciplinaire de Neuroscience (IINS) UMR 5297 CNRS/Université de Bordeaux