What is the function of ZO-1?
Zona Occludens 1 (ZO-1) is a tight junction (TJ) protein found in complexes at cell–cell contacts. The role of ZO-1 is to recruit other TJ proteins.1,2 The resulting TJ complexes regulate paracellular flow, contribute to apical-basal polarity, and are part of signaling pathways for proliferation and differentiation.3 This protein is useful for highlighting cell–cell contacts both in cultured cells and in tissue samples, outlining cell membranes and specific structures.
Where is ZO-1 expressed?
The protein is localized to the cytoplasmic membrane in most types of cells, particularly where a barrier function is essential. It is common in endothelial cells,4 which line the internal surface of blood and lymph vessels, and in epithelial cells,5 which form the outer barrier of organs.
ZO-1 is expressed in many tissues including the intestine, kidney, liver, and skeletal muscle cells.
What proteins does ZO-1 interact with?
The molecular weight of ZO-1 is 220kDa6 and it contains multiple distinct protein domains that allow bind to other junctional proteins at the cytoplasmic membrane. The N-terminal of ZO-1 can dimerize with other ZO proteins and bind directly to other TJ proteins including claudins, connexions, and JAMs,7–10 which allows it to assemble TJ complexes. The C-terminal can interact with actin and cortactin, anchoring the TJ complexes to the cytoskeleton.8,11 This suggests that ZO-1 forms a link between the outer cell–cell contacts and the inner actin.
1. McNeil, E., Capaldo, C. T. & Macara, I. G. Zonula occludens-1 function in the assembly of tight junctions in Madin-Darby canine kidney epithelial cells. Mol. Biol. Cell 17, 1922–32 (2006).
2. Kratzer, I. et al. Complexity and developmental changes in the expression pattern of claudins at the blood-CSF barrier. Histochem. Cell Biol. (2012). doi:10.1007/s00418-012-1001-9
3. Guillemot, L., Paschoud, S., Pulimeno, P., Foglia, A. & Citi, S. The cytoplasmic plaque of tight junctions: A scaffolding and signalling center. Biochim. Biophys. Acta - Biomembr. 1778, 601–613 (2008).
4. Tornavaca, O. et al. ZO-1 controls endothelial adherens junctions, cell-cell tension, angiogenesis, and barrier formation. J. Cell Biol. 208, 821–38 (2015).
5. Umeda, K. et al. Establishment and characterization of cultured epithelial cells lacking expression of ZO-1. J. Biol. Chem. 279, 44785–94 (2004).
6. Stevenson, B. R. Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia. J. Cell Biol. 103, 755–766 (1986).
7. Itoh, M. et al. Direct Binding of Three Tight Junction-Associated Maguks, Zo-1, Zo-2, and Zo-3, with the Cooh Termini of Claudins. J. Cell Biol. 147, 1351–1363 (1999).
8. Fanning, A. S., Jameson, B. J., Jesaitis, L. A. & Anderson, J. M. The Tight Junction Protein ZO-1 Establishes a Link between the Transmembrane Protein Occludin and the Actin Cytoskeleton. J. Biol. Chem. 273, 29745–29753 (1998).
9. Kausalya, P. J., Reichert, M. & Hunziker, W. Connexin45 directly binds to ZO-1 and localizes to the tight junction region in epithelial MDCK cells. FEBS Lett. 505, 92–96 (2001).
10. Itoh, M. et al. Junctional adhesion molecule (JAM) binds to PAR-3. J. Cell Biol. 154, 491–498 (2001).
11. Itoh, M., Nagafuchi, A., Moroi, S. & Tsukita, S. Involvement of ZO-1 in Cadherin-based Cell Adhesion through Its Direct Binding to α Catenin and Actin Filaments. J. Cell Biol. 138, 181–192 (1997).