ZO-1 Polyclonal antibody

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?

ZO-1 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,^6-10 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.

What is the molecular weight of ZO-1?

ZO-1 has an apparent molecular weight of 210-225 kDa. There are two isoforms of ZO-1, α⁺ and α^-, which are produced by alternative RNA splicing and differ in the presence or absence of an internal 80-amino acid domain^12,13. In some literature, the bands with a molecular weight of 250-260 kDa can also be detected for ZO-1^14,15,16,17.

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).  
12. Balda MS, Anderson JM. Two classes of tight junctions are revealed by ZO-1 isoforms. Am J Physiol. 264, (4 Pt 1):C918-24 (1993).

13. Sheth B, Fesenko I, Collins JE, Moran B, Wild AE, Anderson JM, Fleming TP. Tight junction assembly during mouse blastocyst formation is regulated by late expression of ZO-1 alpha+ isoform. Development. 124, (10):2027-37(1997).
14. Lassiter R, Merchen TD, Fang X, Wang Y. Protective Role of Kynurenine 3-Monooxygenase in Allograft Rejection and Tubular Injury in Kidney Transplantation. Front Immunol. 7, 12:671025 (2021). 

15. Rempe RG, Hartz AMS, Soldner ELB, Sokola BS, Alluri SR, Abner EL, Kryscio RJ, Pekcec A, Schlichtiger J, Bauer B. Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction in Epilepsy. J Neurosci. 2, 38(18):4301-4315 (2018).

16. Lin SC, Way EL. Effects of morphine and B-endorphin on Ca2+-ATPase activity of synaptic plasma membranes. NIDA Res Monogr. 75, 117-20(1986). 

17. Wu Z, Mirza H, Teo JD, Tan KS. Strain-dependent induction of human enterocyte apoptosis by blastocystis disrupts epithelial barrier and ZO-1 organization in a caspase 3- and 9-dependent manner. Biomed Res Int. 2014, 209163(2014).