Willott E, Balda MS, Fanning AS, Jameson B, Van Itallie C, Anderson JM.. The tight junction protein ZO-1 is homologous to the Drosophila discs- large tumor suppressor protein of septate junctions. Proc Natl Acad Sci USA 90: 7834-7838

Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 09/1993; 90(16):7834-8. DOI: 10.1073/pnas.90.16.7834
Source: PubMed


Tight junctions form an intercellular barrier between epithelial cells, serve to separate tissue compartments, and maintain cellular polarity. Paracellular sealing properties vary among cell types and are regulated by undefined mechanisms. Sequence of the full-length cDNA for human ZO-1, the first identified tight junction component, predicts a protein of 1736 aa. The N-terminal 793 aa are homologous to the product of the lethal(1)discs-large-1 (dlg) tumor suppressor gene of Drosophila, located in septate junctions, and to a 95-kDa protein located in the postsynaptic densities of rat brain, PSD-95. All three proteins contain both a src homology region 3 (SH3 domain), previously identified in membrane proteins involved in signal transduction, and a region homologous to guanylate kinase. ZO-1 contains an additional 943-aa C-terminal domain that is proline-rich (14.1%) and contains an alternatively spliced domain, whose expression was previously shown to correlate with variable properties of tight junctions. dlg mutations result in loss of apical-basolateral epithelial cell polarity and in neoplastic growth. These results suggest a protein family specialized for signal transduction on the cytoplasmic surface of intercellular junctions. These results also provide biochemical evidence for similarity between invertebrate septate and vertebrate tight junctions. The C-terminal domain of ZO-1, and its alternatively spliced region, appears to confer variable properties unique to tight junctions.

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    • "The component of the PAR complex, aPKC, is apically localized and participates in maintenance of apical-lateral polarity. aPKC can recruit the PAR3-PAR6 complex from tight junction sites to subapical region; as a result, PAR3 is excluded from tight junction sites, allowing for tight junction formation 28. ZO1, located on the plasma membrane surface at sites of the cell-cell junction 29, is a well-known organizer for tight junction and notable epithelial marker 30. ZO1 interacts with ZO2 and ZO3 via their PDZ2 domains to form a tight junctional complex. "
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    • "MAGUKs originally referred to a group of cell junction proteins composed of synaptic scaffold protein PSD-95 from mammals, DLG tumour suppressor from Drosophila, and tight junction protein ZO-1 from mammalian epithelia (Cho et al, 1992; Willott et al, 1993; Woods and Bryant, 1993). The family has since grown to encompass a large number of scaffold proteins that play critical roles in diverse cellular processes including inter-cellular connections, cell polarity development and maintenance, synaptic plasticity, and cell survival in multicellular eukaryotes (Funke et al, 2005; Velthuis et al, 2007; Mendoza et al, 2010). "
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    • "Membrane proteins such as cell adhesion molecules, receptors, and channels form functional clusters within selective subcellular regions by binding to PDZ domains [2-5]. Furthermore, some PDZ proteins also anchor specific cytosolic proteins such as protein kinases, cytoskeleton-regulating enzymes and second-messenger-producing enzymes [2,6], and hence, contribute to precise signal transduction between extracellular and intracellular spaces at specific sites such as postsynaptic densities in neurons [2,7], immunological synapses in T-lymphocytes [8,9] and tight junctions in endothelial and epithelial cells [1,10]. "
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