Outside in: inversion of cell polarity controls epithelial lumen formation

Abstract

Establishment of cell polarity is important for epithelial lumen formation, and the molecular mechanisms directing this process are only partially understood. In this issue of Developmental Cell, Bryant et al. (2014) show that disassembly, membrane translocation, and reassembly of podocalyxin complexes controls epithelial cell polarization and lumen formation in 3D matrices.

Figure 1. Podocalyxin-Dependent Polarity Inversion Controls Epithelial Lumen Formation

Podocalyxin (Podxl) and its interacting partners, NHERF1, NHERF2, and Ezrin (Ezr), control lumen formation via polarity inversion in 3D matrices. Integrin signaling through a2b1 and a3b1 leads to FAK and p190A RhoGap activation and RhoA inactivation. This signal, in conjunction with PKC activation, leads to disassembly of Podxl/NHERF1/Ezr complexes at the basal membrane (BM). Membrane translocation events lead to nascent assembly of pre-apical membrane surfaces called apical membrane initiating sites (AMIS), which then mature into apical membranes (AP) during lumen formation between multiple epithelial cells. Podxl associates with NHERF2 during vesicular trafficking, while Podxl/NHERF1/Ezr complexes reform during apical membrane assembly in a manner dependent on the protein phosphatase, PP2A.