Role of lipids in the organization of tight junction

Abstract Cell membrane structures are supramolecular complexes that require the ordered assembly of membrane proteins and lipids. The morphology of various cell adhesion structures in multicellular organisms, such as those between epithelial cells, neural synapses and immune synapses, was initially described through electron microscopic analyses. Subsequent studies aimed to catalog their constituent proteins, which encompass transmembrane cell adhesion molecules, cytoskeletal proteins and scaffolding proteins that bind the two components. However, the diversity of plasma membrane lipids and their significance in the organization of cell adhesion structures were underappreciated until recently. It is now understood that phase separation of lipids and liquid–liquid phase separation of proteins are important driving forces for such self-assembly. In this review, we summarized recent findings on the role of lipids as scaffolds for supramolecular complexes using tight junctions in epithelial cells as an example.