Membrane Lipids in Epithelial Polarity: Sorting out the PIPs

The development of cell polarity in epithelia, is critical for tissue morphogenesis and vectorial transport between the environment and the underlying tissue. Epithelial polarity is defined by the development of distinct plasma membrane domains: the apical membrane interfacing with the exterior lumen compartment, and the basolateral membrane directly contacting the underlying tissue. The de novo generation of polarity is a tightly regulated process, both spatially and temporally, involving changes in the distribution of plasma membrane lipids, localization of apical and basolateral membrane proteins, and vesicular trafficking. Historically, the process of epithelial polarity has been primarily described in relation to the localization and function of protein 'polarity complexes.' However, a critical and foundational role is emerging for plasma membrane lipids, and in particular phosphoinositide species. Here, we broadly review the evidence for a primary role for membrane lipids in the generation of epithelial polarity and highlight key areas requiring further research. We discuss the complex interchange that exists between lipid species and briefly examine how major membrane lipid constituents are generated and intersect with vesicular trafficking to be preferentially localized to different membrane domains with a focus on some of the key protein-enzyme complexes involved in these processes.