Genetic tuning of actin remodelling at the plasma membrane
Research in my lab focuses on the dissection of the molecular mechanisms driving actin network formation in cell edge protrusion, for instance during migration or specific types of host-pathogen interaction. In this talk, I will focus on our recent efforts aimed at characterizing how Rac-subfamily GTPases stimulate Arp2/3 complex-dependent actin network formation through direct interactions with and activation of WAVE Regulatory Complex (WRC). Subunits of WRC and its regulators are disrupted either individually or simultaneously, and consequences and relevance of their interactions explored performing rescue experiments with wildtype versus mutated variants of respective genes. I will demonstrate that these technologies allow analysing and restoring actin-dependent cellular mechanisms with unprecedented flexibility, like using a toolbox, and concerning both qualitative and quantitative aspects of the interactions between members of the pathway. Finally, I will discuss the relevance of such approaches for both fundamental research and for increasing our molecular understanding of the clinical symptoms developed by patients harbouring specific subunit mutations.