Project 07

Dynamics of membrane receptor clustering in endothelial cells

Principle Investigator: Prof. Dr. Amparo Acker-Palmer

Research Areas: Molecular and Cellular Neurobiology

Summary

The spatial organization of transmembrane receptors is a critical step in propagation of signals and receptor trafficking in cells. The largest subfamily of receptor tyrosine kinases (RTK), Eph receptors (Ephs) and their ligands ephrins, are a prototypical example of membrane signaling hubs organized by homotypic multimeric clustering. Moreover, we have shown that the ephrinB ligands emerge as nucleation seeds controlling the clustering, trafficking, and ultimately function of many other receptors at the membrane involving homotypic Ephrin clusters and heterotypic complexes at the cell membrane. Here, we will specifically characterize using super-resolution microscopy the dynamic spatial arrangement of the different components of such homotypic and heterotypic complexes. We will also investigate how these arrangements are regulated at the membrane, recruiting cytosolic adaptors to achieve a variety of efficient functional outcomes. In particular, we will study these complexes in endothelial cells since the signaling derived from these molecular interactions has a functional role in angiogenesis and blood-brain barrier formation.