The Src Homology 3 Domain Is Required for Junctional Adhesion Molecule Binding to the Third PDZ Domain of the Scaffolding Protein ZO-1

Nomme, J.; Fanning, Alan S.; Caffrey, Michael; Lye, Ming F.; Anderson, James M.; Lavie, A.

doi:10.1074/jbc.m111.304089

Cited by 67 publications

(82 citation statements)

References 35 publications

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“…There were no neutral loss ions, which is common on higher charge state peptides as is observed here, which made these assignments much more straightforward. B, structure of ZO-1 from Nomme et al (33) pointing out in blue the Thr-770/772 residues located in the GUK domain. C and D. HUVECs that were transiently transfected with empty vector (EV) or GFP-tagged recombinant ZO-1 (rZO-1) expression vector, with and without mutations T770A, T772A, or T770A/T772A and grown to confluence, were quiesced and treated with vehicle or 0.1 M 15(S)-HETE for 30 min; cell extracts were prepared and immunoprecipitated (IP) with anti-GFP antibodies, and the immunocomplexes were analyzed by WB with the antibodies of the indicated proteins.…”

Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Tight Junctions and Barrier Function Are Disrupted by 15(S)-Hydroxyeicosatetraenoic Acid Partly via Protein Kinase Cϵ-mediated Zona Occludens-1 Phosphorylation at Threonine 770/772

Chattopadhyay

Dyukova

Singh

et al. 2014

Journal of Biological Chemistry

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Background: Tight junctions play an essential role in the maintenance of endothelial barrier function. Results: 15(S)-HETE stimulated ZO-1 phosphorylation at Thr-770/772 residues in PKC⑀-dependent MEK1-ERK1/2 activation disrupting endothelial tight junctions and barrier function. Conclusion: PKC⑀ by interrupting ZO-1 and occludin interactions plays a role in 15(S)-HETE-induced endothelial TJ disruption. Significance: 12/15-Lipoxygenase appears to be a crucial player in the modulation of endothelial barrier permeability.

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Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Tight Junctions and Barrier Function Are Disrupted by 15(S)-Hydroxyeicosatetraenoic Acid Partly via Protein Kinase Cϵ-mediated Zona Occludens-1 Phosphorylation at Threonine 770/772

Chattopadhyay

Dyukova

Singh

et al. 2014

Journal of Biological Chemistry

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“…For example, the src homology 3 (SH3) domain modulates the affinity of the adjacent MAGI1 PDZ3. 11,12 Another example is the third PDZ domain of PSD-95 (PDZ3), which contains an α helix located at the C-terminus outside of the canonical PDZ fold 13 (Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

Interactions outside the Boundaries of the Canonical Binding Groove of a PDZ Domain Influence Ligand Binding

et al. 2012

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“…In the second (Model 2), the interface was formed between the acidic surface of CC and regions of the ZO-1 U5 and GuK domain (17)(18)(19). The crystal structures of ZO-1 PSG and SH3-GuK domains (20)(21)(22) seemed to support the Model 2, since the surface of the GuK domain is largely basic (Fig. 1B).…”

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confidence: 78%

The occludin and ZO-1 complex, defined by small angle X-ray scattering and NMR, has implications for modulating tight junction permeability

Tash¹,

Bewley²,

Russo

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Tight junctions (TJs) are dynamic cellular structures that are critical for compartmentalizing environments within tissues and regulating transport of small molecules, ions, and fluids. Phosphorylation-dependent binding of the transmembrane protein occludin to the structural organizing protein ZO-1 contributes to the regulation of barrier properties; however, the details of their interaction are controversial. Using small angle X-ray scattering (SAXS), NMR chemical shift perturbation, cross-saturation, in vitro binding, and site-directed mutagenesis experiments. we define the interface between the ZO-1 PDZ3-SH3-U5-GuK (PSG) and occludin coiled-coil (CC) domains. The interface is comprised of basic residues in PSG and an acidic region in CC. Complex formation is blocked by a peptide (REESEEYM) that corresponds to CC residues 468-475 and includes a previously uncharacterized phosphosite, with the phosphorylated version having a larger effect. Furthermore, mutation of E470 and E472 reduces cell border localization of occludin. Together, these results localize the interaction to an acidic region in CC and a predominantly basic helix V within the ZO-1 GuK domain. This model has important implications for the phosphorylation-dependent regulation of the occludin∶ZO-1 complex.membrane-associated guanylate kinase | tricellulin | calmodulin T ight junctions (TJs) are highly polarized gates that control the flux of fluids, proteins, and even ions across sheets of endothelial or epithelial cells (1, 2). These barriers function in a range of tissues, including the vasculature of the central nervous system, kidney, and gut epithelium. Dysregulation of barrier properties is associated with a host of disease states including cancer, stroke, diabetic retinopathy, and inflammatory bowel syndrome (3-5). Furthermore, viral and bacterial pathogens exploit specific TJ proteins to gain access to host cells. Thus, understanding the contribution of TJ components in barrier formation and regulation may aid the development of therapies to restore barrier properties, control barrier properties to promote drug delivery to regions of the CNS, and for the development of novel antibacterial and antiviral compounds.Occludin is an integral membrane, vesicle-trafficking, MAL and related proteins for vesicle trafficking and membrane link (MARVEL) protein (6), that has a role in regulating TJ properties (7). For example, in endothelial cells, it regulates TJ barriers in response to cytokines, such as IFN-γ (8, 9), and growth factors, such as VEGF (10). Removal of the cytoplasmic C-terminal coiled coil domain (CC; residues 413-522) of occludin leads to cytoplasmic localization with increased tracer flux through the junctions and an inability to maintain the apical localization of marker proteins (11,12), identifying the CC as a key element in regulation (13). The CC directly associates with the SH3-U5-GuK domains of the membrane-associated guanylate kinase homolog (MAGUK) protein, . ZO proteins are characterized by their core PDZ3-SH3-GuK (PSG) doma...

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The Src Homology 3 Domain Is Required for Junctional Adhesion Molecule Binding to the Third PDZ Domain of the Scaffolding Protein ZO-1

Cited by 67 publications

References 35 publications

Vascular Endothelial Tight Junctions and Barrier Function Are Disrupted by 15(S)-Hydroxyeicosatetraenoic Acid Partly via Protein Kinase Cϵ-mediated Zona Occludens-1 Phosphorylation at Threonine 770/772

Vascular Endothelial Tight Junctions and Barrier Function Are Disrupted by 15(S)-Hydroxyeicosatetraenoic Acid Partly via Protein Kinase Cϵ-mediated Zona Occludens-1 Phosphorylation at Threonine 770/772

Interactions outside the Boundaries of the Canonical Binding Groove of a PDZ Domain Influence Ligand Binding

The occludin and ZO-1 complex, defined by small angle X-ray scattering and NMR, has implications for modulating tight junction permeability

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