Establishment of plasma membrane domain identity in epithelial cells

Principal investigator: Honigmann

Epithelial cells are polarized into apical, lateral and basal plasma membrane domains, each providing important functions in tissue. How the identity of the polarized membrane domains is established is not understood on the mechanistic level. The emerging picture is that interactions between cell adhesion proteins, membrane scaffolding proteins (PAR proteins) and the acto-myosin cortex play a pivotal role in creating positive/negative feedback loops, which lead to global separation of components at the cell membrane and polarized trafficking of internal membranes. In this scheme phosphoinositide lipids are central players, because they provide species specific anchoring points for many membrane associated proteins. PIP(4,5)2 is a key determinant of the apical domain, while PIP(3,4,5)3 is enriched at the basolateral domain. Although the importance of differential distribution of PIP species in epithelial cells is established, it is not clear how this distribution is set-up. In this project we propose to investigate the connection between PIP converting enzymes and cell adhesion proteins as an initial symmetry breaking event in epithelial polarization.