Tight Junction Proteins

Overview of Tight Junctions

  • Definition: Tight junctions are specialized connections between epithelial or endothelial cells that regulate paracellular permeability and maintain cell polarity.

  • Functions:

    • Barrier to solute and water flow.

    • Fence between apical and basolateral membrane domains.

    • Signaling hubs regulating cell proliferation and differentiation.

Re-formation of Tight Junctions after Calcium Depletion; Endogenous NG-ZO1 in a Confluent MDCK-II Monolayer. Cell Press, Karina et al., 2019

 Scaffolding & Cytoplasmic Proteins

These link transmembrane proteins to the cytoskeleton and signaling machinery.

🧩 ZO-1 (Zonula Occludens-1)

  • Role: Central scaffolding protein that links claudins and occludin to the actin cytoskeleton.

  • Domains: Contains PDZ, SH3, and GUK domains for protein-protein interactions.

🧩 ZO-2 and ZO-3

  • Similar to: ZO-1

  • Function: Redundant and overlapping roles in junction assembly and maintenance.

🧩 Afadin

  • Connects: Tight junctions and adherens junctions.

  • Function: Regulates polarity and junctional integrity.

🧩 Cingulin

  • Role: Binds actomyosin cytoskeleton and regulates RhoA signaling.

  • Location: Cytoplasmic plaque of tight junctions.

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Endogenous concentration of ZO1 and ZO2 in Tight Junctions and Cytoplasm. Cell Press, Karina et al., 2019