Structure, biochemistry, and assembly of epithelial tight junctions

Area of Science:

• Cell biology
• Epithelial biology
• Membrane biophysics

Background:

• The zonula occludens (ZO), or tight junction, is essential for epithelial barrier function.
• It controls paracellular diffusion of molecules and ions, influencing electrical resistance.
• ZO also segregates apical and basolateral membrane domains by restricting lateral diffusion.

Purpose of the Study:

• To elucidate the structural basis and molecular composition of the zonula occludens.
• To investigate the dynamic nature and assembly mechanisms of tight junctions.
• To identify key proteins involved in tight junction formation and function.

Main Methods:

• Freeze-fracture electron microscopy (EM) to visualize ZO strand number.
• Transmission EM for ultrastructural analysis.
• Biochemical and molecular approaches to identify associated proteins like ZO-1.

Main Results:

• Tight junction strand number correlates with paracellular electrical resistance.
• ZO is not a membrane fusion but a protein-mediated apposition of plasma membranes.
• Emerging evidence points to ZO-1 and other proteins as key components, with dynamic assembly involving cytoskeletal elements.

Conclusions:

• The zonula occludens is a complex protein structure critical for epithelial integrity and polarity.
• Tight junction assembly is a dynamic process potentially involving interactions with the cytoskeleton and other junctional components.
• Further research is needed to fully understand the molecular mechanisms underlying tight junction formation and regulation.