Uncoupling of the molecular 'fence' and paracellular 'gate' functions in epithelial tight junctions

Abstract

DURING epithelial morphogenesis, the establishment of tight junctions precedes the development of both the asymmetry in protein and lipid composition between apical and basolateral cell surfaces (the 'fence' function) and the restriction in the transport of ions and nonelectrolytes through the extracellular clefts between cells (the 'gate' function)^1,2. Molecular models that explain both functions envision strands of particles extending as rings in the cell's perimeter that interact with similar strands located at the apposing cell^2–5. This model accounts for the 'fence' function, because the strands prevent diffusion of protein and lipids, and also for the 'gate' function, because the interaction between strands minimizes the width of the extracellular clefts, increasing transepithelial resistance to ions and decreasing non-electrolyte permeability. Here we describe the results of energy depletion, which for the first time separates both functions: it abolishes the gate function, as determined by the dramatic decrease in transepithelial resistance, but it leaves the fence function intact, as determined by the maintenance of lipid polarity.