Polarized cell migration

Polarized cell migration is a tightly regulated mechanism that occurs in many processes. The Rho-family GTPases, the WASP family proteins and the Arp2/3 complex play a key role in establishing cell polarization through the actin cytoskeleton. The main focus of my project is the investigation of how cell migration is orchestrated by the interactions between WAVE2, a member of the WASP family proteins, and its interactors.

 

 

 

 

 

 

 

 

 

 

 

 

De novo actin polymerization generates the forces driving many biological processes, including directional movement of lamellipodia, endocytosis of membrane receptors and macromolecules, and recycling/supply of membranes at the cell edge. In vivo, actin nucleators, i.e. the Arp2/3 complex and Formins, including Drfs (Diaphanous-related formins), are essential for the formation of new actin filaments. My main points of interest are novel protein complexes and mechanisms that are involved in regulating the activity of these two distinct classes of actin nucleators.

 

 

 

 

 

 

 

 

 

 

 

 

POTENTIAL REGULATORS OF WAVE2 DEPENDENT CELLULAR PROCESSES

WAVE2 is an ubiquitously expressed WASP-family Verprolin homologous protein and an important component of WAVE complex. Its activation downstream of Rac GTPase leads to the activation of Arp2/3 complex, actin polymerization and formation of Rac-dependent membrane protrusions (lamellipodia). WAVE2 was identified as interactor and substrate of an ubiquitously expressed kinase. I am interested in the interaction between these two proteins, both on biochemical (mapping the interaction and phosphorylation sites) and cellular level (how does WAVE2 phosphorylation affects the formation of Rac-dependent membrane protrusions).