Soutenance de thèse de Mme Perrine Verdys - Fernand Gallais Conference Room

PhD Thesis committee:

• Prof. Dr. Eva Kiermaier, LIMES Institute, University of Bonn, Germany - Referee
• Dr. Emmanuelle Planus, Institut pour l'Avancée des Biosciences, Université Grenoble Alpes, Grenoble, France - Referee
• Dr. Pablo Vargas, INSERM - Institut Necker Enfants Malades, Paris, France - Referee
• Prof. Christel Lutz, Université Toulouse III - Paul Sabatier, Toulouse, France - Examiner
• Dr. Renaud Poincloux, HDR, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France – PhD supervisor
• Prof. Sébastien Carréno, Institut de Recherche en Immunologie et cancérologie, Université de Montréal, Canada - PhD co-supervisor
• Dr. Véronique Le Cabec, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France – Invited member

Abstract

The actin-rich cellular cortex serves as a mechanical support and plays a key role in a diversity of cellular structures involved in numerous functions, including cell division and migration. The three proteins of the ERM family, ezrin, radixin, and moesin, are direct linkers between the plasma membrane and the actin cytoskeleton, and are described as being central in these processes. However, the function, respective contributions, and redundancy of the three ERM proteins has not been challenged in macrophages, innate immune cells that migrate through tissues to maintain immune surveillance and tissue homeostasis. To address this important question, we developed single and triple ERM KO macrophages, and show that neither the single nor the triple knock-out of ERM proteins has any effect on macrophage migration in a diversity of contexts, including in vivo diapedesis or the infiltration through healthy derma or tumoral tissue. Importantly, macrophages devoid of ERM are still capable of forming the different actin structures involved in migration, namely filopodia, lamellipodia, podosomes, and membrane ruffles. Finally, we show that neither the structure nor the mechanics of the macrophage actin cortex are affected by ERM depletion. Our results, therefore demonstrate that ERM proteins are dispensable for macrophage migration and cortex organization, which challenges the established model of the universal role of these proteins.