A2 Chavakis Dimmeler

Integrins are heterodimeric receptors mediating adhesion to extracellular matrix proteins and are integral for tissue morphogenesis. Integrin-mediated adhesivity is regulated by intracellular signaling. However, the signaling pathways regulating integrin activity and function in endothelial cells are unclear. Moreover, the role of these signaling pathways for angiogenesis is not established so far. In our previous investigations we found an important role of the small GTPase Rap1a for angiogenic sprouting, migration, integrin-regulation, adhesion and in vivo angiogenesis. The aim of the present project is to investigate: 1) the role of RAPL, an effector of Rap1a, for the regulation of integrin activity and endocytosis in endothelial cells, and 2) the role of the emerging new integrin-associating proteins, kindlins (specifically kindlin-2, and -3), for angiogenic features such as adhesion, migration, in vivo tip cell formation and angiogenesis.